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Interferon-alpha-Induced Changes in NODDI Predispose to the Development of Fatigue.

N G Dowell1, S Bouyagoub1, J Tibble2

  • 1Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9RR, UK.

Neuroscience
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Interferon-alpha (IFN-α) treatment can cause fatigue by altering brain microstructure. Acute changes in the striatum

Keywords:
cytokinedepressiondiffusion MRIfatigueinflammation

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Area of Science:

  • Neuroscience
  • Immunology
  • Radiology

Background:

  • Interferon-alpha (IFN-α) is crucial for antiviral immunity and treats hepatitis C.
  • IFN-α therapy can cause mood, motivation, and cognitive impairments, resembling depression.
  • Early fatigue and motivational issues in patients are linked to basal ganglia (striatal) changes.

Purpose of the Study:

  • To investigate if diffusion MRI metrics (NODDI) can predict IFN-α-induced fatigue.
  • To explore the relationship between striatal microstructural changes and fatigue development.

Main Methods:

  • Used neurite orientation dispersion and density imaging (NODDI) on multi-shell diffusion MRI.
  • Acquired MRI and blood samples at baseline and 4 hours post-first IFN-α injection.
  • Monitored 18 patients for 12 weeks, assessing fatigue and mood symptoms.

Main Results:

  • IFN-α induced acute fatigue and an increase in neurite density index (NDI) in the brain.
  • Increased NDI correlated with simultaneous fatigue development.
  • Acute striatal microstructural changes predicted later fatigue, but not mood symptoms.

Conclusions:

  • NODDI shows potential as an in vivo biomarker for IFN-α's central nervous system effects.
  • The striatum is highly sensitive to IFN-α, and its perturbation contributes to fatigue.
  • Striatal microstructural changes are early indicators of IFN-α-induced fatigue.