Structural Correlates for Fatigue in Early Relapsing Remitting Multiple Sclerosis

Objectives: Fatigue is a common symptom in multiple sclerosis (MS) patients, even early in the disease, but the pathophysiology remains unclear. We aimed to determine morphologic and microstructural correlates and neuropsychological parameters of cognitive fatigue in early relapsing-remitting MS patients.

Methods: Seventy-nine early relapsing-remitting MS patients (38 with fatigue and 41 without), none of whom suffered from depression, underwent neuropsychological testing. Magnetic resonance imaging was performed using anatomical and diffusion tensor imaging sequences on all patients and 40 controls. Voxel-based morphologic analysis and tract-based spatial statistics were performed.

Results: Only patients with cognitive fatigue, but not those without, exhibited alterations in the thalamic region, showing reduced thalamic fractional anisotropy and increased mean diffusivity values. No differences in lesion volume and lesion distribution were observed between patient groups. In cognitive tests, no significant differences were found between the two groups in the number of patients with pathologic scores; however, subjective cognitive impairment differed.

Conclusion: Morphological alterations and distinct microstructural changes (mainly in the thalamus) but not typical MS lesions were found to be related to cognitive fatigue in early MS. We suggest that compensatory processes adapting to these changes could initially facilitate normal cognitive performance, but also result in a feeling of fatigue.

Key Points: • Morphological alterations and microstructural changes are related to fatigue in multiple sclerosis • Thalamic alterations in particular were related to fatigue in early MS • Fatigued patients exhibited subjective but not measurable cognitive impairment • Compensatory processes help preserve or maintain cognitive performance but also contribute to fatigue.