‘Burned-out MS’ (BOMS) is a term that has arisen recently in the multiple sclerosis literature. An early definition of BOMS described patients with a high EDSS score after a prolonged course of illness who had atrophy but no inflammatory activity on MRI (Bhatia & Singh. Ann Indian Acad Neurol 2019;22:131-136). The MS Association of America described BOMS as a form of inactive MS in which disease progression slows dramatically later in life. This is not a new phenotype since these definitions overlap with that of stable disease (not active/without progression) in the 2013 revisions (Lublin et al. Neurology 2014;83:278-286). The key difference and controversy is that BOMS presumes that no further MS-related progression will occur.

The only published paper on the topic used the descriptor ‘benign/burnt-out MS’, which compounded one controversial term with another (McFaul et al. Neurol Neuroimmunol Neuroinflamm 2021;8:e960). The study was a health database analysis, so the term was less about clinical measures than about checkboxes; the goal was to identify people who could safely stop their disease-modifying therapy (DMT). As such, benign/burned-out MS was defined as an RRMS patient with immunosenescence at low risk of transitioning to SPMS. Curiously, the authors acknowledged that other authors have defined BOMS as progressive MS that has stopped progressing, but specifically excluded these patients from their analysis.

Alternatively, in his online blog, Gavin Giovannoni described BOMS as no disability worsening after a period of smouldering-associated worsening (SAW) (https://gavingiovannoni.substack.com/p/does-burnt-out-ms-exist). SAW was largely equated with paramagnetic rim lesions (PRL), although PRLs are not detectable in many MS patients (Kwong et al. PLoS One 2021;16:e0256845). Moreover, it is likely that PRLs, which are characterized by deposition of iron-rich microglia/macrophages and remyelination failure, do not fully capture the breadth and heterogeneity of progressive biology.

A suggestion is that BOMS represents the resolution of PRLs that is known to occur in some MS patients (Dal-Bianco et al. Brain 2021;144:833-847). However, it is unclear if iron loss at the lesion edge is due to tissue repair and lesion shrinkage, or to severe tissue loss (Mainero & Treaba. AJR Am J Roentgenol 2021;217:1010. This needs to be understood more fully before PRL resolution or BOMS onset can be used as biomarkers of treatment success.

A further concern is that any late-phase progression that occurs in BOMS patients may be attributed to age-related changes since, by definition, the MS has burned itself out and no disease activity will henceforth be detectable. This would justify discontinuing DMTs, as the study cited above concluded (McFaul 2021), but this may be premature. It is conceivable that other pathophysiological changes are occurring that are undetected by current methods and which contribute to late-phase progression. More information is needed on the full range of pathologies that can occur in MS – and how to detect them in routine clinical practice. Moreover, other criteria may prove more useful than BOMS when deciding whether to discontinue a DMT in older MS patients.