2017.01.04
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.）
Konno T1,2, Yoshida K3, Mizuno T4, Kawarai T5, Tada M2, Nozaki H6, Ikeda SI7, Nishizawa M2, Onodera O8, Wszolek ZK1, Ikeuchi T9.
1Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
2Department of Neurology, Niigata University.
3Department of Brain Disease Research, Shinshu University School of Medicine.
4Department of Neurology, Kyoto Prefectural University of Medicine.
5Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School.
6Department of Medical Technology, School of Health Sciences Faculty of Medicine, Niigata University.
7Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine.
8Department of Molecular Neuroscience, Niigata University.
9Department of Molecular Genetics, Brain Research Institute, Niigata University.
Abstract
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.
