Time course of lesion-induced atrophy in multiple sclerosis

J Neurol. 2022 Aug;269(8):4478-4487. doi: 10.1007/s00415-022-11094-y. Epub 2022 Apr 8.


Background and purpose: White matter (WM) tract disruption impacts volume loss in connected deep gray matter (DGM) over 5 years in people with multiple sclerosis (PwMS). However, the timeline of this phenomenon remains poorly characterized.

Materials and methods: Annual serial MRI for 181 PwMS was retrospectively analyzed from a 10-year clinical trial database. Annualized thalamic atrophy, DGM atrophy, and disruption of connected WM tracts were measured. For time series analysis, ~700 epochs were collated using a sliding 5-year window, and regression models predicting 1-year atrophy were applied to characterize the influence of new tract disruption from preceding years, while controlling for whole brain atrophy and other relevant factors.

Results: Disruptions of WM tracts connected to the thalamus were significantly associated with thalamic atrophy 1 year later (β: 0.048-0.103). This effect was not observed for thalamic tract disruption concurrent with the time of atrophy nor for thalamic tract disruption preceding the atrophy by 2-4 years. Similarly, disruptions of white matter tracts connected to the DGM were significantly associated with DGM atrophy 1 year later (β: 0.078-0.111), but not for tract disruption concurrent with, nor preceding the atrophy by 2-4 years.

Conclusion: Increased rates of thalamic and DGM atrophy were restricted to 1 year following newly developed disruption in connected WM tracts. In research and clinical settings, additional gray matter atrophy may be expected 1 year following new lesion growth in connected white matter.

Keywords: Atrophy; Degeneration; Lesions; Multiple sclerosis.

MeSH terms

  • Atrophy / pathology
  • Brain / diagnostic imaging
  • Brain / pathology
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Multiple Sclerosis* / complications
  • Multiple Sclerosis* / diagnostic imaging
  • Multiple Sclerosis* / pathology
  • Retrospective Studies
  • White Matter* / diagnostic imaging
  • White Matter* / pathology