ArticleJournal of neurology2026
Beyond dissemination criteria: lesion-based longitudinal MRI of atypical demyelinating lesions at the boundary of multiple sclerosis.
Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundRevisions of the McDonald diagnostic criteria have improved the sensitivity of multiple sclerosis (MS) diagnosis by incorporating MRI-based dissemination in space and time. However, some inflammatory demyelinating lesions fulfill dissemination criteria while showing radiological features atypical for MS, even in the absence of anti-AQP4 and anti-MOG antibodies. The long-term radiological course of these atypical idiopathic inflammatory demyelinating lesions (AIIDLs) remains unclear.
methodsWe retrospectively analyzed 39 Japanese patients with AIIDLs, classified into multiple spotty lesions (MSLs), disseminated encephalomyelitis-like lesions (DEMLs), leukoencephalopathy-like lesions (LELs), and tumefactive lesions (TLs), and compared them with 97 patients with radiologically typical MS. Longitudinal MRI analyses evaluated lesion morphology, distribution, volume, and central vein sign (CVS) positivity, together with clinical outcomes and treatment responses.
resultsOver a mean follow-up of 11 years, 38 of 39 AIIDL cases (97.4%) retained radiologically atypical features despite clinical relapses and fulfillment of dissemination criteria. MSLs and TLs lacked canonical MS features, such as periventricular lesions and T1 hypointense black holes. Only one case with LELs evolved into typical MS. CVS positivity exceeding 40% was observed in two MSLs cases but lesions remained atypical in distribution. Lesion volumes differed significantly among subgroups, with smaller volumes in MSLs and larger volumes in LELs compared with typical MS. Corticosteroids, immunosuppressants, and B cell depletion therapies appeared to be associated with clinical stabilization in several AIIDL subtypes, whereas conventional MS disease-modifying therapies were less consistently effective.
conclusionsIn this cohort, most AIIDLs retained radiologically atypical brain MRI features over long-term follow-up despite recurrent inflammatory demyelinating events. These findings suggest that dissemination-based criteria alone may not fully capture the radiological heterogeneity of AQP4-IgG- and MOG-IgG-negative demyelinating disorders. Longitudinal lesion-based MRI phenotyping may provide complementary information for diagnostic reassessment although external validation and integration with optic nerve, spinal cord, and biological markers are required.
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