Evidence for multiple sclerosis as an infectious disease

California Medicine, 1972

An animal model for acute multiple sclerosis (MSa) is experimental allergic encephalomyelitis (EAE). EAE is produced by intradermal injection of a protein component of central nervous system (CNS) myelin. Ultrastructural studies of EAE and of a peripheral nerve analog, experimental allergic neuritis (EAN), have revealed an orderly sequence of cellular events leading to the destruction and removal of myelin with sparing of axons (primary demyelination). Acute MS has not been studied electron microscopically, but the ultrastructural similarities between EAN and a case of acute Landry-Guillain-Barre syndrome, a primary demyelinating disease of the peripheral nervous system, suggest that a similar sequence of events might be found in acute MS. While the pathological findings support a cellmediated or delayed hypersensitivity response, there is also evidence for the pathogenetic role of circulating antibodies. Among such evidence is included the finding that sera from animals with EAE and humans with acute MS rapidly produce a reversible block of complex (polysynaptic) electrical activity when applied to CNS tissue cultures, which suggests a possible mechanism for transient symptoms in Ms. Epidemiological and other studies link MS with a viral cause, although no direct evidence that MS is caused by a virus exists. Viral and immunological mechanisrs are not mutually exclusive in considering pathogenetic possibilities for MS, for it can be postulated that a viral infection of the central nervous system acts as a triggering agent for a series of immune responses, including production of a bioelectric blocking antibody and demyelination mediated by sensitized cells, the combination of which ultimately produces the total clinical picture of MS.

The Lancet Neurology, 2005

Reviews in Medical Virology, 2000

Multiple sclerosis (MS) is a chronic, demyelinating disease of the CNS in which autoimmunity to myelin plays a role in pathogenesis. The epidemiology of MS indicates that it may be triggered by a virus infection before the age of adolescence, but attempts to associate a speci®c virus with MS have produced equivocal results. Many studies of the aetiology of MS have postulated that a persistent virus infection is involved, but transient virus infection may provide a plausible alternative mechanism that could explain many of the inconsistencies in MS research. The most studied animal model of MS is chronic relapsing experimental autoimmune encephalomyelitis (CREAE), which is induced in susceptible animals following injection of myelin components. While CREAE cannot provide information on the initiating factor for MS, it may mimic disease processes occurring after an initial trigger that may involve transient virus infection. The disease process may comprise separate triggering and relapse phases. The triggering phase may involve sensitisation to myelin antigens as a result of damage to oligodendrocytes or molecular mimicry. The relapse phase could be similar to CREAE, or alternatively relapses may be induced by further transient virus infections which may not involve infection of the CNS, but which may involve the recrudescence of anti-myelin autoimmunity. Although current vaccines have a high degree of biosafety, it is suggested that the measles-mumps-rubella vaccine in particular could be modi®ed to obviate any possibility of triggering anti-myelin autoimmunity.

QJM: An International Journal of Medicine, 1994

CNS Drugs, 1999

Multiple sclerosis (MS) is a chronic disease of the CNS that typically begins in late adolescence or early adulthood. It is highly variable in its expression and severity. The cause of MS is unknown, but both genetic and environmental factors have been implicated in its pathogenesis. It is known that viruses can induce chronic neurological disease, but the pathogenetic process in unclear. A viral cause for MS has been postulated, but to date no single virus has been confirmed to be associated with the disease. Although most viral candidates are no longer considered as possible aetiological agents in MS, a few are still being investigated.

Current neurology and neuroscience reports, 2003

Viruses have been major players in the search for the cause of multiple sclerosis (MS). In support of the viral theory is the predominance of CD8+ T cells and class-I major histocompatibility complex in lesions, the powerful therapeutic effects of beta interferons, the ease of inducing demyelination in experimental models following virus challenge, and the documented examples of several human demyelinating diseases conclusively demonstrated to be of viral origin. We propose two hypotheses of how viruses may cause MS. In the "Hit-Hit" hypothesis, the virus persists or may be reactivated in the central nervous system (CNS). Injury is the result of direct viral damage and by an attempt of the immune response to clear the infectious agent. In the "Hit-Run" hypothesis, virus infects the periphery but never enters the CNS. The virus sets up an abnormal immunologic milieu for subsequent autoimmunity. In both scenarios, knowing the inciting virus would be expected to eli...

Cerebrospinal Fluid Analysis in Multiple Sclerosis, 1996

Neuroimmune Pharmacology, 2008

Journal of autoimmune diseases, 2006

Epidemiological data suggest the notion that in Multiple Sclerosis (MS) is an acquired autoimmune disease and the cause may be an environmental factor(s), probably infectious, in genetically susceptible individuals. Several cases of viral induced demyelinatimg encephalomyelitis in human beings and in experimental models as well as the presence of IgG oligoclonal bands in the cerebrospinal fluid indicate that the infectious factor may be viral. However, the absence of a specific virus identification in MS central nervous system may hardly support this notion. On the other hand, the partial response of patients with MS to immunosuppressive and immunomodulatory therapy support the evidence of an autoimmune etiology for MS. However, the autoimmune hypothesis shares the same criticism with the infectious one in that no autoantigen(s) specific to and causative for MS has ever been identified. Nevertheless, the absence of identifiable infectious agent, especially viral does not rule out its presence at a certain time -point and the concomitant long term triggering of an autoimmune cascade of events thereafter. Several concepts have emerged in an attempt to explain the autoimmune mechanisms and ongoing neurodegeneration in MS on the basis of the infectious -viral hypothesis.

Acta Neurologica Belgica, 2007

Financial support: 'Nationaal fonds voor wetenschappelijk onderzoek Vlaanderen (FWO)'