Background The pathogenesis of large demyelinating lesions is still controversial. Atypical tumefactive demyelinating lesions (TDL) associated with acute inflammation, peri-lesional oedema and gadolinium ring enhancement are infrequently described in patients with juvenile-onset multiple sclerosis (MS).

Objective To describe the clinical, imaging and micro-structural metrics of TDLs and chronic MS lesions in patients with juvenile-onset MS.

Methods Ten patients diagnosed with MS were analysed for the presence of TDLs and chronic non enhancing MS lesions. The MS lesions were defined by a region of interest encircling the lesion centre on 2–3 consecutive slices. DTI images were acquired along 31 independent orientations using a single shot echo-planar imaging sequence.

Results Four patients with 6 TDL, developed acute neurological symptomatology. The two girls presented with acute ataxia and aphasia, and the two boys with severe ataxia. Three patients progressed rapidly to develop seizures, became stuporotic and were admitted to the paediatric intensive care unit. Brain MRI demonstrated six TDLs. Analysis of the whole group (10 patients) disclosed 21 chronic non enhancing lesions. Assessment of DTI metrics of TDL as compared to chronic MS lesions disclosed significant differences.

Conclusion TDL are a possible presentation of demyelinating disorders, posing a diagnostic and therapeutic dilemma towards neoplastic lesions. The micro-structural analysis of TDL suggests a severe tissue disruption probably due to the acute inflammatory process and oedema. Our analysis provides metrical tools that together with MR spectroscopy and perfusion may aid to identify accurately TDLs, potentially sparing young patients unnecessary and possibly debilitating brain biopsy.