Haematopoietic stem cell transplantation in CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a severe neurodegenerative disease leading to death usually within a few years after symptoms onset.1 Patients present with cognitive decline, behavioural changes and pyramidal signs in the context of patchy white matter lesions. ALSP is a primary microgliopathy caused by haploinsufficiency of the colony-stimulating factor 1 receptor (CSF1R). CSF1R is critical for the development, maintenance and activation of microglia. We hypothesised that haematopoietic stem cell transplantation (HSCT) can be relevant in ALSP by correcting CSF1R loss-of-function in microglia. We provide the first prospective report of a patient with ALSP with a 30-month follow-up after a successful HSCT. We present in parallel the clinical outcome of a consecutive patient with similar age, sex and disease course who did not undergo HSCT. Patient 1 was in her early 30s when she developed leg stiffness after a mild head trauma. Her mother died of a rapidly progressive neurological disorder before age 40. Brain MRI revealed patchy and asymmetrical T2/FLAIR white matter hyperintensities (online supplementary file 1A) and T1 hypointensities. She was first misdiagnosed with multiple sclerosis. ALSP was then suspected because of the family history and hyperintense white matter lesions on diffusion weighted imaging (DWI). CSF1R - targeted analysis revealed a c.2498C>A, p.Thr833Lys mutation. ### Supplementary data [jnnp-2019-320701supp001.pdf] A repeat brain MRI showed progression of T2/FLAIR (online supplementary file 1A) and DWI white matter lesions. Neuropsychological testing revealed mild alterations in executive and working memory …