Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation

Eur J Neurol. 2017 Jan;24(1):37-45. doi: 10.1111/ene.13125. Epub 2016 Sep 29.


Background and purpose: The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated.

Methods: Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data.

Results: In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18-78 years), the mean age at death was 53 years (range 23-84 years) and the mean disease duration was 6.8 years (range 1-29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158-11.177). There was an age-dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion-restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy-nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype-genotype correlations.

Conclusions: The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.

Keywords: adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; colony stimulating factor 1 receptor; hereditary diffuse leukoencephalopathy with spheroids; leukoencephalopathy; pigmented orthochromatic leukodystrophy.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Axons / pathology
  • Corpus Callosum / diagnostic imaging
  • Corpus Callosum / pathology
  • Female
  • Heterozygote
  • Humans
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / genetics*
  • Leukoencephalopathies / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Movement Disorders / etiology
  • Movement Disorders / physiopathology
  • Mutation / genetics
  • Neuroglia / pathology
  • Penetrance
  • Pyramidal Tracts / diagnostic imaging
  • Pyramidal Tracts / pathology
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Sex Characteristics
  • White Matter / diagnostic imaging
  • White Matter / pathology
  • Young Adult


  • CSF1R protein, human
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor