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The sequence of structural, functional and cognitive changes in multiple sclerosis.

Iris Dekker1, Menno M Schoonheim2, Vikram Venkatraghavan3

  • 1Amsterdam UMC, Location VUmc, Departments of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117, Amsterdam, The Netherlands; Neurology, MS Center Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117, Amsterdam, The Netherlands.

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Summary
This summary is machine-generated.

Grey matter atrophy in multiple sclerosis (MS) occurs early, while white matter changes and cognitive decline manifest later. This study maps the sequence of MS disease events for better patient monitoring.

Keywords:
CognitionDisabilityDisease progressionEvent-based modellingMRIMultiple sclerosis

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Area of Science:

  • Neuroscience
  • Medical Imaging
  • Biostatistics

Background:

  • Multiple sclerosis (MS) disease progression and its underlying mechanisms remain incompletely understood.
  • Identifying the sequence of clinical and imaging events is crucial for effective patient management.

Purpose of the Study:

  • To investigate the temporal sequence of biomarker abnormalities in multiple sclerosis (MS) progression.
  • To understand the order of physical disability and cognitive impairment milestones in MS.
  • To apply a novel data-driven approach to model MS disease trajectory.

Main Methods:

  • Analysis of a cohort comprising 295 relapse-onset MS patients and 96 healthy controls.
  • Utilized 28 features including T2-lesion load, regional brain/spinal cord volumes, functional centrality, white matter integrity, and cognitive test performance.
  • Employed a discriminative event-based model to determine the sequence of biomarker abnormalities.

Main Results:

  • Grey matter (GM) atrophy in the cerebellum and thalamus, and corticospinal tract changes are early MS events.
  • White matter tract integrity and cognitive functions (working memory, attention, executive function) are affected later in the disease course.
  • Early functional changes in the default-mode network and spinal cord volume were observed compared to the general MS population.

Conclusions:

  • Data-driven modeling elucidated the sequence of imaging and non-imaging events in MS progression.
  • Findings provide insights into MS disease propagation mechanisms.
  • The study enables fine-grained patient staging for improved monitoring and management of multiple sclerosis.