The role of disconnection in explaining disability in multiple sclerosis

Caterina Lapucci, Simona Schiavi, Alessio Signori, Elvira Sbragia, Giulia Bommarito, Maria Cellerino, Antonio Uccelli, Matilde Inglese, Luca Roccatagliata, Matteo Pardini

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: In multiple sclerosis, the correlation between white matter lesion volumes (LV) and expanded disability status scale (EDSS) is at best moderate, leading to the “clinico-radiological paradox”, influenced by many factors, including the lack of information on the spatial localisation of each lesion on synthetic metrics such as LV. We used a probabilistic approach to provide the volume of WM tracts that may be disconnected by lesions and to evaluate its correlation with EDSS. Methods: Forty-five patients (aged 37.4 ± 6.8 years, mean ± standard deviation; 30 females; 29 relapsing-remitting, 16 progressive) underwent 3-T magnetic resonance imaging. Both LV and the volume of the tracts crossing the lesioned regions (disconnectome volume, DV) were calculated using BCBtoolkit and correlated with EDSS. Results: T1-weighted LV and DV significantly correlated with EDSS (p ≤ 0.006 r ≥ 0.413) as it was for T2-weighted LV and T2-weighted DV (p ≤ 0.004 r ≥ 0.430), but only T1-weighetd and T2-weighted DVs were EDSS significant predictors (p ≤ 0.001). The correlations of T1-weighted and T2-weighted LV with EDSS were significantly mediated by DV, while no effect of LV on the EDSS-DV correlation was observed. Conclusion: The volume of disconnected WM bundles mediates the LV-EDSS correlation, representing the lonely EDSS predictor.

Original languageEnglish
Article number23
JournalEuropean radiology experimental
Issue number1
StatePublished - Dec 2022
Externally publishedYes


  • Diffusion tensor imaging
  • Disability evaluation
  • Magnetic resonance imaging
  • Multiple sclerosis
  • White matter


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