Imaging features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: a case report.

BACKGROUND

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, progressive white matter disorder caused by pathogenic variants in the CSF1R gene. It typically presents in mid-adulthood with progressive cognitive, motor, and neuropsychiatric decline, but its phenotypic variability often leads to delayed diagnosis.

CASE PRESENTATION: We describe a 41-year-old woman with no prior neurological history or relevant psychiatric tendencies who developed progressive cognitive impairment, urinary incontinence, gait disturbance, and sleep disruption over 3-4 years. Brain MRI revealed confluent frontoparietal and periventricular white matter hyperintensities with sparing of the posterior fossa and temporal lobes, chronic non-vascular diffusion restriction in the bilateral corona radiata and thinning of the corpus callosum. CT demonstrated punctate calcifications in the inferior corpus callosum. Genome sequencing identified a paternally inherited heterozygous pathogenic variant in the CSF1R gene (c.2344C>T; p.Arg782Cys), confirming ALSP.

DISCUSSION: ALSP results from microglial dysfunction leading to impaired myelin maintenance, chronic axonal injury, and reactive pigmented macrophage infiltration. The corpus callosum, due to its dense myelination, is particularly vulnerable, explaining its characteristic atrophy and calcifications. Persistent, non-vascular DWI restriction distinguishes ALSP from many mimics, including AARS2-related leukoencephalopathy, which typically lacks calcifications and presents earlier. Recognition of these imaging features is essential for timely access to genetic testing and confirmatory diagnosis.

CONCLUSION

ALSP should be considered in adults with progressive neuropsychiatric symptoms and compatible imaging findings. Awareness of hallmark MRI and CT features-particularly corpus callosum calcifications and non-vascular diffusion restriction-can expedite genetic testing, improve diagnostic accuracy, and guide patient care.