Abstract / Summary
Abstract Background: Baló's concentric sclerosis (BCS) is a rare inflammatory demyelinating disorder characterized by concentric layers of alternating demyelinated and relatively myelin-preserved tissue. BCS shares pathological and radiological features with multiple sclerosis (MS) and tumefactive demyelinating lesions (TDLs). However, it remains unclear whether MS, BCS, and TDLs belong to a shared mechanistic spectrum.
Methods: We developed a seven-variable reaction-diffusion model incorporating resting and activated macrophages and microglia, normal and damaged oligodendrocytes, pro-inflammatory and anti-inflammatory cytokines, and a neuroprotective astrocyte-like component. We used sensitivity analyses to test whether parameter variations could generate MS, BCS, and TDL patterns. We compared simulated BCS patterns with quantitative radial profiles of Klüver-Barrera-stained sections from three autopsy BCS cases and examined post-onset modulation of selected lesion-promoting and protective pathways.
Results: Within a single framework, the model generated MS, BCS, and TDL patterns. Increasing either oligodendrocyte vulnerability or the inflammatory activity of macrophages and microglia shifted lesion morphology from the small MS pattern through the concentric BCS pattern to the broadly expanding TDL pattern, with the BCS pattern emerging mainly at intermediate values. The simulated BCS pattern exhibited several spatial features similar to those observed in pathological specimens. Earlier interventions produced greater suppression of lesion expansion than delayed interventions, while enhancement of protective or anti-inflammatory pathways also reduced lesion expansion.
Conclusions: These findings support the possibility of a shared mechanistic spectrum across MS, BCS, and TDLs. Oligodendrocyte vulnerability and the inflammatory activity of macrophages and microglia may contribute to the formation of demyelinating lesion patterns. The simulations further suggested that earlier intervention and enhancement of protective or anti-inflammatory pathways may more effectively suppress lesion progression. This framework may provide a clinically relevant perspective for interpreting BCS and TDLs in relation to MS.