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Cerebellar volume alterations are associated with cognitive dysfunction and fatigue in patients with systemic lupus

Zahra Makdad Najeeb¹, Grégory Kuchcinski^2,3, Kristoffer Alexander Zervides⁴

¹Section of Diagnostic Radiology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.

BMC Rheumatology

|July 3, 2026

Abstract

Background:

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease targeting multiple organ systems, including the nervous system. The cerebellum may be involved in prevalent neuropsychiatric manifestations, such as depression and cognitive dysfunction, alongside other prevalent SLE manifestations such as pain and fatigue. We aim to compare cerebellar volumes in SLE patients and healthy individuals (HI) and assess the correlation between cerebellar volumes and cognitive impairment, fatigue, pain, and depression in SLE.

Methods:

72 female SLE patients and 25 age- and sex-matched HI underwent 3 tesla magnetic resonance imaging (MRI), clinical evaluations, and cognitive testing. T1-weighted MRI scans were segmented using CEREbellum Segmentation (CERES) volBrain automatic segmentation. Extracted cerebellar lobule volumes (normalized to total cerebellar volume) were compared between SLE and HI using analyses of covariance (ANCOVA). In regions showing significant volume changes between SLE and HI, the relationship between volume and clinical scores for cognitive impairment, fatigue, pain, and depression was analyzed using either ANCOVAs or partial correlation analyses.

Results:

Lobular analysis of the cerebellum revealed significant (p < 0.05) region-specific volume alterations in SLE compared with HI. Bilateral and left lobule IV volumes were larger, while bilateral, right, and left lobule VIIB volumes were smaller in SLE compared to HI. Smaller white matter volumes in right lobule VIIIA, and right lobule X and larger white matter volumes in lobule crus I were observed in SLE compared to HI. In SLE, smaller VIIB volumes were significantly correlated with poorer cognitive performance (both complex attention and cognitive flexibility), and with higher fatigue scores.

Conclusion:

The findings suggest that the cerebellum, and particularly lobule VIIB, is involved in SLE and may contribute to both cognitive dysfunction and fatigue in patients with systemic lupus erythematosus.

Trial Registration:

Not applicable.

Keywords:

Cerebellar lobules Cerebellum MRI Systemic lupus erythematous (SLE)

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