Fatigue in early multiple sclerosis: MRI metrics of neuroinflammation, relapse and neurodegeneration

• Published in: Brain communications 2024, Vol.6 (5), p.fcae278
• Main Authors: Meijboom, Rozanna, Foley, Peter, MacDougall, Niall J J, Mina, Yair, York, Elizabeth N, Kampaite, Agniete, Mollison, Daisy, Kearns, Patrick K A, White, Nicole, Thrippleton, Michael J, Murray, Katy, Valdés Hernández, Maria Del C, Reich, Daniel S, Connick, Peter, Jacobson, Steven, Nair, Govind, Chandran, Siddharthan, Waldman, Adam D
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2632-1297; 2632-1297
• DOI: 10.1093/braincomms/fcae278

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease affecting the brain and spinal cord. Fatigue is a common disabling symptom from MS onset, however the mechanisms by which underlying disease processes cause fatigue remain unclear. Improved pathophysiological understanding offers potential for improved treatments for MS-related fatigue. MRI provides insights into neuroinflammatory activity and neurodegeneration, although existing evidence for imaging correlates of MS fatigue is mixed. We explore associations between fatigue and MRI measures in the brain and spinal cord to identify neuroinflammatory and regional neurodegenerative substrates of fatigue in early relapsing-remitting MS (RRMS). Recently diagnosed (/≤36). Disability and depression were assessed with the expanded-disability status scale and Patient Health Questionnaire, respectively. MRI measures were compared between fatigue groups, both cross-sectionally and longitudinally, using regression analyses. Higher disability and depression scores were observed for participants with fatigue, with a higher number of fatigued participants receiving disease-modifying treatments at follow-up. Structural MRI data for brain were available for = 313 (45% fatigued) and for spinal cord for = 324 (46% fatigued). Cervical spinal cord cross-sectional area 2-3, white and grey matter volumes decreased, and WML volume increased, over time for both groups ( < 0.05). However, no significant between-group differences in these measures were found either cross-sectionally or longitudinally ( > 0.05). The presence of new/enlarging WMLs (49% in fatigued; 51% in non-fatigued) at follow-up also did not differ between groups ( > 0.05). Our results suggest that fatigue is not driven by neuroinflammation or neurodegeneration measurable by current structural MRI in early RRMS. This novel negative finding in a large multi-centre cohort of people with recently diagnosed RRMS helps to resolve uncert