Variably protease-sensitive prionopathy mimicking frontotemporal dementia
Variably protease-sensitive prionopathy mimicking frontotemporal dementia
复制标题
DOI：
10.1111/neup.12538
复制
发表时间：
2019-04-01
期刊：
影响因子：
2.3
通讯作者：
Bodi, Istvan
中科院分区：
文献类型：
--
作者：
Aizpurua, Miren;Selvackadunco, Sashika;Bodi, Istvan
散发性Pron病是一种致命性神经退行性疾病，临床特征为快速进行性痴呆和肌阵挛。可变蛋白水解酶敏感型Pron病(VPSPr)是最近发现的一种散发性人类Pron疾病，可能具有漫长的非典型临床病史。在这里，我们描述了一例VPSPr患者，有很长的疑似额颞部痴呆(FTD)病史。一名61岁的男子表现出言语困难，包括命名物体和构建多部分句子，而在理解方面没有困难。运动异常包括轻微的急速追赶、轻微的眼跳和轻快的反应。没有痴呆症的家族病史。后来，他出现吞咽困难，并怀疑FTD合并运动神经元病。他在71岁时去世，他的大脑被捐赠给伦敦神经退行性疾病脑库。大脑(1004克)显示轻度至中度萎缩，主要位于额叶。组织学显示中度海绵状微空泡化主要影响额叶和顶叶皮质，但也可见于基底节和小脑。免疫组织化学染色仅发现轻度阿尔茨海默病，与BrainNet Europe II期一致。反式激活反应DNA结合蛋白43 kDa和α-突触核蛋白免疫染色均为阴性。Prion蛋白(PrP)免疫组织化学染色显示颗粒/突触呈斑块状分布，主要分布在皮质较深部位，在小脑和基底节也可见微斑块。Western blotting证实，在不存在类型1和类型2的情况下，出现了一条低分子量的抗蛋白酶PrP条带，并呈微弱的阶梯状。这些特征是VPSPr的诊断依据。VPSPr可以模拟各种神经退行性疾病；诊断需要PrP免疫组织化学和Western blotting。在没有其他神经退行性病变的情况下出现片状海绵状改变应引起对VPSPr的怀疑，即使是在有漫长临床病史的老年患者中也是如此。
Sporadic prion diseases are fatal neurodegenerative disorders characterized clinically by rapidly progressive dementia and myoclonus. Variably protease-sensitive prionopathy (VPSPr) is a recently identified sporadic human prion disorder that may present with a lengthy atypical clinical history. Here, we describe a case of VPSPr in a patient with a long history of suspected frontotemporal dementia (FTD). A 61-year-old man presented with speech difficulties, including naming objects and constructing multipart sentences, while there was no difficulty in comprehension. Movement abnormalities included slightly jerky pursuit, minor dysmetria of saccades and brisk reflexes. There was no family history of dementia. Later he developed swallowing difficulties and the possibility of FTD with motor neuron disease was suspected. He died at the age of 71 and his brain was donated to the London Neurodegenerative Diseases Brain Bank. The brain (1004 g) showed mild to moderate atrophy, predominantly in the frontal lobe. Histology revealed moderate spongiform microvacuolation mostly affecting the frontal and parietal cortices, but also present focally in the basal ganglia and the cerebellum. Only mild Alzheimer pathology was found by extensive immunohistochemistry, in keeping with BrainNet Europe stage II. Trans-activation response DNA-binding protein 43 kDa and alpha-synuclein immunostains were negative. Immunostaining for prion protein (PrP) showed granular/synaptic positivity in a patchy distribution, mainly within the deeper cortex, and also revealed microplaques in the cerebellum and basal ganglia. Western blotting confirmed a low molecular weight protease-resistant PrP band with a faint ladder-like pattern in the absence of types 1 and 2 isoforms. These features are diagnostic of VPSPr. VPSPr can mimic various neurodegenerative conditions; diagnosis requires both PrP immunohistochemistry and Western blotting. The presence of patchy spongiform change in the absence of other neurodegenerative pathology should raise suspicion of VPSPr, even in elderly patients with a lengthy clinical history.