Association of subcortical structural shapes with fatigue in neuromyelitis optica spectrum disorder


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Although fatigue is a major symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), the underlying mechanism remains unclear. We explored the relationship between subcortical structures and fatigue severity to identify neural substrates of fatigue in NMOSD. Clinical characteristics with brain magnetic resonance imaging were evaluated in forty patients with NMOSD. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) questionnaire (a higher score indicates less fatigue). We assessed the correlation between subcortical structures and fatigue severity using surface-based shape analysis. Most of the enrolled patients showed fatigue (72.5%; mean FACIT-fatigue score, 34.8 ± 10.8). The FACIT-fatigue score was negatively correlated with Expanded Disability Status Scale and Beck Depression Inventory scores (r = − 0.382, p = 0.016; r = − 0.578, p < 0.001). We observed that the right thalamus was the only extracted region for various threshold experiments. Further, patients with lower FACIT-fatigue scores (more fatigue) had decreased local shape volume in the right thalamus. Fatigue is common in patients with NMOSD, and atrophy in the right thalamus is strongly correlated with fatigue severity. The local shape volume of the right thalamus might serve as a biomarker of fatigue in NMOSD.

The thalamus is involved in regulating several brain functions, including motor, sensory, and higher cortical functions, and acts as a gateway between cortical and subcortical areas13,14. The relationship between the thalamus and fatigue has been studied in patients with MS. Several neuropathological and neuroimaging studies have reported the involvement of thalamus in MS13,21,22, and dysfunction of the cortico-subcortical pathway with thalamus atrophy is considered as a major substrate of fatigue in patients with MS2,10,13. Besides the morphological alterations, some authors suggested that the microstructural changes of the thalamus assessed by diffusion tensor imaging (DTI) could also be related to fatigue in the early stages of MS23. And the others showed DTI parameters from cortex, especially right temporal cortex, correlated with thalamic atrophy and fatigue severity24. Multimodal MRI studies of fatigue in NMOSD are needed to find more precise imaging biomarkers for fatigue.
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