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Biopsy histopathology in the diagnosis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)

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Abstract

Aim

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an inherited rare disease affecting young adults. We present the clinical, imaging, and neuropathological results of our case series, emphasizing biopsy histology combined with clinical information will increase the accuracy of early diagnosis.

Methods

In total, 4 females and 2 male ALSP patients with onset at ages 24–45 years were enrolled. Clinical manifestations, neuroimaging, and histopathology as well as gene mutation were analyzed and compared with literature.

Results

Clinical manifestations include cognitive decline with/without psycho-behavior problems and movement disorders including paralysis, hemiplegia, parkinsonism, and pyramidal tract injury, as well as dysarthria, dysphagia, and sensory disturbances. MRI showed multiple periventricular and subcortical white matter lesions, involving the corpus callosum, with no enhancement, but with persistent hyperintensity on diffuse-weighted imaging. Histology showed widespread white matter damage and pale stain, especially destroyed axons with spheroids and funicular axons which were stained with neurofilament and ubiquitin. Foamy and pigmented macrophages were another typical change. CSF1R mutation was found in 4 of them. All of the patients were misdiagnosed and treated for a long time for multiple sclerosis, cerebral infarction, normal pressure hydrocephalus, etc.

Conclusion

ALSP will cause rapidly progressing dementia with/without movement disorders in young adults. The definite diagnosis should be based on a comprehensive analysis of clinical manifestations, and neuroimaging, histology, and genetic results. Early biopsy will add to the accuracy of the diagnosis.

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Funding

This work was supported by Chinese Academy of Medical Sciences Innovation fund for medical sciences (2016-I2M-1-004), National Natural Science Foundation of China (81550021), 13th Five year National Key Research and Development Program of China (2016YFC1306300), and the strategic priority research program (Pilot study) “Biological Basis of Aging and Therapeutic Strategies” of the Chinese Academy of Sciences (grant XDPB10).

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Authors and Affiliations

  1. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science/Peking Union Medical College, 1st, Dongcheng District, Beijing, 100730, China

    Chenhui Mao, Lixin Zhou, Yingmai Yang, Jingwen Niu, Jie Li, Xinying Huang, Haitao Ren, Yanhuan Zhao, Bin Peng & Jing Gao

  2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science/Peking Union Medical College, Beijing, China

    Liangrui Zhou

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  1. Chenhui Mao
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  2. Liangrui Zhou
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Correspondence to Jing Gao.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (PUMC ethics committee 2017006) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Mao, C., Zhou, L., Zhou, L. et al. Biopsy histopathology in the diagnosis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Neurol Sci 41, 403–409 (2020). https://doi.org/10.1007/s10072-019-04116-7

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  • DOI: https://doi.org/10.1007/s10072-019-04116-7

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