Objective: To characterize the clinical and neuropathological factors associated with brain atrophy in CSF1R-related disorder (CSF1R-RD).

Background: CSF1R-RD is a rare, fatal autosomal dominant leukoencephalopathy caused by pathogenic variants in the CSF1R gene, which primarily impair microglial function. The disorder is characterized by white matter neurodegeneration, progressive brain atrophy, and the presence of axonal spheroids and pigmented glial cells.

Method: Clinical variables analyzed included age at disease onset, sex, presenting clinical symptoms, disease duration, survival, type of initial symptom onset (cognitive or motor impairment), and mutation type. Neuropathological factors included the severity of brain atrophy and the presence of concomitant neuropathology associated with other neurodegenerative diseases, such as Alzheimer’s disease or Parkinson’s disease. The association between clinical and neuropathological variables and brain atrophy severity was evaluated using Spearman correlation analysis.

Results: Brain atrophy was categorized into three stages: mild, severe, and very severe. A significant positive correlation was observed between the severity of brain atrophy and disease duration (r = 0.62, p = 0.03). In addition, a positive trend was noted between brain atrophy severity and disease onset with cognitive impairment (r = 0.51, p = 0.08).

Conclusion: Brain atrophy severity increases with the duration of CSF1R-RD. Cognitive impairment at disease onset may be associated with more severe brain atrophy in individuals with CSF1R-RD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-clinical-and-neuropathological-factors-associated-with-brain-atrophy-in-csf1r-rd/