Lesion burden determines the incremental diagnostic value of intrathecal IgG oligoclonal bands synthesis in multiple...

The 2024 revision of the McDonald criteria allows the diagnosis of multiple sclerosis (MS) based on dissemination in space alone when ≥4 typical lesion locations are present, raising the question of how lesion burden influences the incremental diagnostic value of cerebrospinal fluid (CSF) analysis.

To evaluate the incremental diagnostic value of intrathecal IgG oligoclonal bands (IgGOB) according to lesion burden at MS diagnosis.

In this retrospective, cross-sectional, single-centre study, 341 patients undergoing diagnostic evaluation for suspected MS were included. Logistic regression models assessed the associations among lesion burden, intrathecal IgG synthesis and MS diagnosis.

Lesion burden was strongly associated with MS diagnosis (β = 1.55, p < 0.0001). CSF-restricted IgGOB positivity was associated with lesion burden, but not with disease duration. In a multivariable logistic regression model, both lesion burden (p < 0.0001) and CSF-restricted IgGOB (p < 0.0001) remained independently associated with MS diagnosis (AUC = 0.988). The incremental diagnostic contribution of intrathecal IgG synthesis progressively decreased as lesion burden increased.

The incremental diagnostic value of intrathecal IgG synthesis is strongly influenced by lesion burden. These findings support a context-dependent interpretation of CSF analysis within the 2024 McDonald diagnostic criteria.