Altered Intrinsic Brain Activity In Patients With CSF1R-Related Leukoencephalopathy

Abstract Objective: CSF1R-related leukoencephalopathy is an adult-onset white matter disease with high disability and mortality, while current diagnostic approaches are prone to misdiagnosis and not sensitive enough for pre-clinical alternations. This study introduced amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) based on resting-state functional MRI (rsfMRI) to compare the spontaneous brain activities of patients and healthy controls, aiming to provide early clues for disease onset and enhance our understanding of the disease.Methods: RsfMRI was performed on 11 patients and 23 healthy controls and preprocessed for calculation of ALFF and ReHo. Permutation tests with threshold free cluster enhancement (number of permutations =5,000) was applied for comparison. Voxels with P value<0.05 (family-wise error corrected) and cluster size>10 voxels was considered with significant difference.Results: Compared to controls, the patient group showed decreased ALFF in right paracentral lobule and precentral gyrus, and increased ALFF in left dorsolateral superior frontal gyrus, left postcentral gyrus, left precentral gyrus, right precuneus, as well as bilateral insula, parahippocampal gyrus, hippocampus, midbrain and cingulate gyrus. Decreased ReHo was found in bilateral supplementary motor area and paracentral lobule of patients, while ReHo increased in right superior occipital gyrus, right precentral gyrus, left angular gyrus, as well as bilateral parahippocampal gyrus, hippocampus, middle occipital gyrus, supramarginal gyrus and extra-nuclear.Conclusion: These results revealed altered spontaneous brain activities in CSF1R-related leukoencephalopathy, especially in limbic system and supplementary motor area, which may serve as an early biomarker for the onset, and shed light on disease mechanisms.