Chenhui Mao1, Liangrui Zhou2, Lixin Zhou1, Yingmai Yang1, Jingwen Niu1, Jie Li1, Xinying Huang1, Haitao Ren1, Yanhuan Zhao1, Bin Peng1, Jing Gao3. 1. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science/Peking Union Medical College, 1st, Dongcheng District, Beijing, 100730, China. 2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science/Peking Union Medical College, Beijing, China. 3. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science/Peking Union Medical College, 1st, Dongcheng District, Beijing, 100730, China. gj107@163.com.
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.
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 ALSPpatients 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.
Entities:
Keywords:
ALSP; Axon spheroids; Biopsy; Funicular axons; White matter disease
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