Acute disseminated encephalomyelitis progressing to multiple sclerosis: Are infectious triggers involved?

Abstract

Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) are demyelinating disorders affecting the central nervous system. An autoimmune aetiology has been proposed for both. ADEM principally affects adolescents following acute infection by a variety of pathogens and has also been reported to occur following vaccination. ADEM typically resolves following medical treatment, whereas MS follows a more relapsing and remitting course. The pathogenesis of MS remains unclear, but it is thought that a combination of infectious and non-infectious environmental factors and host genetics act synergistically to cause disease. A variety of viruses, including Epstein Barr virus, cytomegalovirus, herpes simplex virus and varicella zoster virus, have been implicated as possible infectious triggers. The similar clinical and pathological presentation of ADEM and MS presents a diagnostic challenge for distinguishing ADEM from a first episode of MS. Some cases of ADEM progress to MS for reasons that are not currently clear. This review examines the evidence for infectious agents as triggers for ADEM progressing to MS and suggests potential methods that may facilitate identification of infectious agents that may be responsible for the pathogenesis of ADEM to MS.

An interferon-β-resistant and NLRP3 inflammasome–independent subtype of EAE with neuronal damage

“…Here, we intentionally used an agent, which is not Mtb, to test our hypothesis -- strong stimulation of innate immunity enhances Type-B EAE responses – is not specific for the Mtb adjuvant. Murine gamma herpesvirus-68 (MHV-68), equivalent to Epstein - Barr virus (EBV) in humans, was used simply because of the relevance of EBV infection to MS 11 . Type-A EAE induction accompanied with a high inoculum of MHV-68 made mice develop NLRP3 inflammasome-independent and IFNβ-resistant EAE (Figure 1g).…”

Herpes simplex virus‐induced anti‐N‐methyl‐d‐aspartate receptor encephalitis: a systematic literature review with analysis of 43 cases

“…9 Other possibilities may involve non-specific B-cell activation and/or molecular mimicry due to shared epitopes between HSV and NMDAR, as seen in other neurological diseases such as multiple sclerosis, acute disseminated encephalomyelitis, Guillain-Barr e syndrome, and Sydenham chorea. [52][53][54][55] The possibility of a common genetic predisposition between the two entities may also contribute. 29 Different to the biphasic disease described above (HSE followed by HSV-induced anti-NMDAR encephalitis; Table SII, top part), in patients with HSE with concomitant detection of anti-NMDAR antibodies (in the absence of a clinical episode of anti-NMDAR encephalitis) the pathogenic role of antibodies remains unclear.…”

Glucocorticosteroids: Risk-Benefit Appraisals in Multiple Sclerosis and MS-Associated Optic Neuritis

“…Most adverse effects are presumably subtle and fall into NOAELs, though most patients ultimately cannot tolerate side-effects and require modification of the treatment plan. In any case, an assessment of infections with CNS involvements before and after corticosteroids use would be useful in diagnosis, treatment and management of the disease progression in multiple sclerosis [54]. A summation of some of the above concerns with potential clinical relevance is illustrated in Figure 1 towards a risk stratification and mitigation strategy in multiples sclerosis.…”