Clinical Diagnosis and Differential Diagnosis Between CSF1R- and AARS2-Related Leukoencephalopathy

CSF1R-related leukoencephalopathy (CSF1R-L) and AARS2-related leukoencephalopathy (AARS2-L) were two disease entities sharing similar phenotype and even pathological changes. Although clinically, radiologically, and pathologically similar, they were caused by mutation of two different genes. As the rarity of the two diseases, the differential diagnosis of them was difficult. 23 CSF1R-L and 6 AARS2-L patients were enrolled from the Leukoencephalopathy Clinic, Peking Union Medical College Hospital in China. Detailed clinical information, neuroimaging manifestations, and genetic data were collected and analyzed. Demographically, female patients were more in AARS2-L than CSF1R-L. Clinically, cognitive impairment and emotion/personality change were common in both groups. Bulbar palsy, extrapyramidal symptoms, and hemiplegia/pyramidal impairment were more common in CSF1R-L, while ataxia was significantly more common in AARS2-L. Abnormal menstruation including infertility was significantly more in AARS2-L. Radiologically, similar features were found, including lateral ventricle-centered white matter lesions, involving corpus callosum, avoiding U fibers. The lesions showed persistent hyperintensity on DWI image and were not contrasted after gadolinium enhancement. In CSF1R-L, the lesions could be widespread confluent or patchy and spotted, extending to centrum semiovale and subcortical white matter occasionally, which was significantly different from AARS2-L. Besides, brain stem lesion caused by pyramidal degeneration, spotted or linear calcification and obviously brain atrophy were common in CSF1R-L. In AARS2-L, periventricular white matter rarefaction was significantly common. No genotype and phenotype association was found in these two diseases. Although similar, there were several clinical and radiological features helping differentiating the two distinct diseases.