Early Pathologic Changes in Hereditary Diffuse Leukoencephalopathy With Spheroids
Early Pathologic Changes in Hereditary Diffuse Leukoencephalopathy With Spheroids
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DOI：
10.1097/nen.0000000000000139
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发表时间：
2014-12-01
影响因子：
3.2
通讯作者：
Yoshida, Mari
中科院分区：
文献类型：
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作者：
Riku, Yuichi;Ando, Takashi;Yoshida, Mari
遗传性弥漫性白质脑病伴球状体（HDLS）是一种家族性神经退行性疾病，临床表现为进行性认知和运动功能障碍。最近在HDLS患者中发现了集落刺激因子1受体（CSF 1 R）基因突变。弥漫性轴索球状体、髓鞘丢失和白色物质中的色素沉着小胶质细胞是HDLS的病理学标志;然而，HDLS患者的早期病理学发现尚未被描述。我们报告一个日本家庭HDLS。一种新的杂合子c.在63岁死亡的女性先证者中发现了CSF 1 R基因的653 C>Y突变;尸检结果与HDLS一致。我们也解剖了她的妹妹，她被认为是神经学上无症状的，死于肺结核，享年44岁。尸检显示斑片状轴突变性和髓鞘丢失，主要发生在皮质下白色物质中。着色的小胶质细胞弥漫分布在整个大脑的白色物质和表达CSF 1 R差。总之，我们的观察结果表明，HDLS的病理可能最初的特点是在皮质下白色物质区域的多灶性病变。此外，色素沉着的小胶质细胞很少表达CSF 1 R，并且在疾病的早期阶段弥漫性分布在整个白色物质中，在轴突损伤和髓磷脂损失之前。
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a familial neurodegenerative disease clinically characterized by progressive cognitive and motor dysfunction. Mutations in the colony-stimulating factor 1 receptor (CSF1R) gene have recently been identified in HDLS patients. The presence of diffuse axonal spheroids, myelin loss, and pigmented microglia in the white matter are pathologic hallmarks of HDLS; however, early pathologic findings have not been described inHDLS patients. We report a Japanese family with HDLS. A novel heterozygous c. 653 C>Y mutation in the CSF1R gene was identified in the female proband who died at the age of 63 years; postmortem findings were compatible with HDLS. We also autopsied her sister who was considered to be neurologically asymptomatic and died of tuberculosis at the age of 44 years. Postmortem studies revealed patchy axonal degeneration and myelin loss, predominantly in the subcortical white matter. Pigmented microglia were distributed diffusely throughout the cerebral white matter and expressed CSF1R poorly. In conclusion, our observations suggest that the pathology of HDLS may initially be characterized by multifocal lesions in subcortical white matter regions. Moreover, pigmented microglia poorly express CSF1R and are distributed diffusely throughout the white matter at the early disease stage, preceding axonal damage and myelin loss.