What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI

Abstract

Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls. Forty‐eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi‐analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section. From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume. Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain–behavior relationships that are not yet established in adolescence.

Opposite white matter abnormalities in post-infectious vs. gradual onset chronic fatigue syndrome revealed by diffusion MRI

“…Alterations in these diffusion metrics have been observed in various neurological and psychiatric disorders, offering valuable insights into the underlying pathophysiological mechanisms [10][11][12][13][14] . However, previous DTI results for ME/CFS are inconsistent or even contradictory [15][16][17][18][19] , possibly due to bias from small sample sizes or the heterogeneity of ME/CFS. In this study, we investigated the WM in ME/CFS using a rigorous and systematic approach, following recommendations for high reliability in translational research 20 .…”