A Novel Radiographic and Genetic Variant of Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Case Report.

PMID 40936738 | PMCID PMC12420650 | DOI 10.1177/19418744251377118 · The Neurohospitalist · 2025

BACKGROUND: The differential for acute onset progressive leukoencephalopathy in adults is broad. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare genetic white matter disorder with typical onset around 40 years. Variability in clinical presentation can often lead to misdiagnosis with other neurodegenerative disorders, underscoring the importance of taking a detailed medical history, obtaining comprehensive diagnostic evaluations, and considering timely genetic testing. CASE PRESENTATION: A 53-year-old woman with a medical history of systemic lupus erythematosus and marginal zone B-cell lymphoma in remission presented with subacute onset fatigue, confusion, and slurred speech following SARS-CoV2 infection. Diagnostic testing was unremarkable except for elevated CSF interleukin-6, tumor necrosis factor, and myelin basic protein levels. The patient was diagnosed with presumed post-infectious encephalitis. Over the next 2 months, the patient's clinical syndrome progressed to include bradykinesia, hypophonia, dysphagia and resting tremor. Pathology and genetic testing revealed a rare diagnosis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). CONCLUSIONS: This case illustrates a stepwise process for constructing a comprehensive differential diagnosis for acute onset of progressive leukoencephalopathy and a general management strategy. We also report a novel radiographic finding and genetic variant in the CSF1R gene associated with ALSP.