CNS manifestations of Nasu-Hakola disease - A frontal dementia with bone cysts
CNS manifestations of Nasu-Hakola disease - A frontal dementia with bone cysts
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DOI：
10.1212/wnl.56.11.1552
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发表时间：
2001-06-12
期刊：
影响因子：
9.9
通讯作者：
Haltia, M
中科院分区：
文献类型：
--
作者：
Paloneva, J;Autti, T;Haltia, M
背景：Nasu-Hakola病或多囊性脂膜性骨发育不良伴硬化性白质脑病（PLOSL）是一种遗传异质性疾病，其特征是系统性骨囊肿和痴呆的结合。目的：作者介绍了一系列PLOSL患者的神经学，神经放射学和神经病理学分析，其中诊断已被分子遗传学方法证实。方法：对8例患者的临床、神经生理、影像学随访资料及3例患者的尸检标本进行分析。所有8例患者均为DAP12基因的功能缺失突变纯合子。结果。在大多数患者中，该病首次出现的症状是在第三个十年中扭伤后脚踝和手腕疼痛，随后是四肢骨骼囊性病变引起的骨折。额叶综合症和痴呆从30岁开始发展，导致40岁死亡。神经影像学显示，在临床神经症状出现之前，基底节区的双核比异常高且逐渐增加，钙化，tp加权MR图像上白质信号强度增加。三名接受尸检的患者表现为晚期硬化性脑白质病，伴有额叶加重、小胶质细胞广泛激活和微血管改变。结论：虽然plsl患者多数表现为骨折，但部分患者在出现神经系统症状前未表现出任何骨性症状和体征。因此，不明原因的额型痴呆患者应通过踝关节和手腕x线检查。目前的结果表明，早期基底神经节受累于PLOSL。
Background: Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a genetically heterogeneous disease characterized by a combination of systemic bone cysts and dementia. Objective: The authors present a neurologic, neuroradiologic, and neuropathologic analysis of a series of PLOSL patients in which the diagnosis has been confirmed by molecular genetic methods. Methods: Clinical, neurophysiologic, and imaging follow-up data on eight patients as well as autopsy samples of three patients were analyzed in this study. All eight patients were homozygous fora loss-of-function mutation in the DAP12 gene. Results. In most patients, the disease debuted with pain in ankles and wrists after strain during the third decade, followed by fractures caused by cystic lesions in the bones of the extremities. Frontal lobe syndrome and dementia began to develop by age 30, leading to death by age 40. Neuroimaging disclosed abnormally high and progressively increasing bicaudate ratios and calcifications in the basal ganglia as well as increased signal intensities of the white matter on TP-weighted MR images even before the appearance of clinical neurologic symptoms. Three patients who had undergone autopsies showed an advanced sclerosing leukoencephalopathy with frontal accentuation, widespread activation of microglia, and microvascular changes. Conclusions: Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations. Consequently, patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists. The current results suggest early basal ganglia involvement in PLOSL.