Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): Estimation of pathological lesion stage from brain images

Background Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a disease responsible for cognitive impairment in adult humans. It is caused by mutations in the colony stimulating factor 1 receptor gene (CSF1R) or alanyl-transfer (t) RNA synthetase 2 (AARS2) gene and affects brain white matter. Settlement of stages of the pathological brain lesions (Oyanagi et al. 2017) from the findings of brain imaging will be inevitably essential for prognostication. Methods MRI images of eight patients with ALSP were analyzed semiquantitatively. White matter degeneration was assessed on a scale of 0 to 4 (none, patchy, large patchy, confluent, and diffuse) at six anatomical points, and brain atrophy on a scale 0 to 4 (none, slight, mild, moderate, and severe) in four anatomical areas. The scores of the two assessments were then summed to give total MRI scores of 0–40 points. Based on the scores, the MRI features were classified as Grades (0–4). Regression analysis was applied to mutual association between mRS, white matter degeneration score, brain atrophy score, the total MRI score and disease duration. Results White matter degeneration score, brain atrophy score, and the total MRI score were significantly correlated with the disease duration. MRI Grades (2–4) based on the total MRI scores and the features of the images were well correlated with the pathological lesion stages (II - IV); i.e., ‘large patchy’ white matter degeneration in the frontal and parietal lobes (MRI Grade 2) corresponded to pathological Stage II, ‘confluent’ degeneration (Grade 3) to Stage III, and ‘diffuse’ degeneration (Grade 4) to Stage IV. Conclusion MRI Grades (2–4) resulted from the total MRI scores were well correlated with the pathological lesion Stages (II - IV).