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Haematopoietic stem cell transplantation in CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
  1. Fanny Mochel1,2,
  2. Cécile Delorme2,3,
  3. Virginie Czernecki3,
  4. Jerome Froger4,
  5. Florence Cormier2,3,
  6. Emmanuel Ellie5,
  7. Nathalie Fegueux6,
  8. Stéphane Lehéricy2,7,
  9. Serge Lumbroso8,
  10. Raphael Schiffmann9,
  11. Patrick Aubourg10,11,
  12. Emmanuel Roze2,3,
  13. Pierre Labauge12,
  14. Stephanie Nguyen13
  1. 1 Department of Genetics, University Hospital Pitié Salpêtrière, Paris, France
  2. 2 Sorbonne Université, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France
  3. 3 Department of Neurology, University Hospital Pitié Salpêtrière, Paris, France
  4. 4 Department of Physical and Rehabilitation Medicine, Centre Hospitalier Universitaire de Nimes, Nimes, France
  5. 5 Department of Neurology, Centre Hospitalier de la Cote Basque, Bayonne, France
  6. 6 Department of Hematology, Montpellier University Hospital, Montpellier, France
  7. 7 Department of Neuroradiology, University Hospital Pitié Salpêtrière, Paris, France
  8. 8 Department of Biochemistry and Molecular Biology, Nimes University Hospital, Nimes, France
  9. 9 Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, Texas, USA
  10. 10 Department of Paediatric Neurology, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin-Bicetre, France
  11. 11 Inserm U 1169, Universite Paris-Sud, Orsay, France
  12. 12 Department of Neurology, Montpellier University Hospital, Montpellier, France
  13. 13 Hematology Department, Montpellier University Hospital, Montpellier, France
  1. Correspondence to Dr Fanny Mochel, Department of Genetics, University Hospital Pitié Salpêtrière, Paris 75013, France; fanny.mochel{at}

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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.

Patients and methods

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.

Supplemental material


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 …

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  • Contributors Conception and design of the study: FM, RS, PA, ER, PL, SN. Acquisition and analysis of data: FM, CD, VC, JF, FCD, EE, NF, SL, SL, RS, PA, ER, PL, SN. Drafting a significant portion of the manuscript or figures: FM, CD, VC, SN.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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