Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism
Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism
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DOI：
10.1093/brain/awh488
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发表时间：
2005-06-01
期刊：
影响因子：
14.5
通讯作者：
Lees, AJ
中科院分区：
文献类型：
--
作者：
Williams, DR;de Silva, R;Lees, AJ
进行性核上性麻痹(PSP)的临床诊断依赖于特征体征和症状的识别。病理诊断的病例中有一部分没有出现这些典型特征，在生活中很难诊断，并被认为是不典型的PSP。这项研究的目的是检查典型和非典型PSP之间明显的临床二分法，并比较这些组的生化和遗传学特征。在连续103例经病理证实的PSP中，我们通过因子分析确定了两种临床表型，我们将其命名为Richardson综合征(RS)和PSP-帕金森综合征(PSP-P)。RS综合征5例，占54%，以早发性姿势不稳、跌倒、核上性垂直凝视麻痹和认知功能障碍为特征。第二组33例(32%)的特征是起病不对称，震颤，对左旋多巴的初始治疗反应中等，经常与帕金森病(PSP-P)相混淆。14例(14%)不能按此标准分类。在RS中，三分之二的病例是男性，而PSP-P的性别分布是均匀的。RS的病程(5.9年比9.1年，P<；0.001)和死亡年龄(72.1年比75.5年，P=0.001)明显短于PSP-P。从脑桥底部分离出的不溶性缠绕蛋白的亚型组成也有显著差异。RS组平均4重复：3重复tau比率为2.84，PSP-P为1.63(P<0.003)。H1H1PSP易感基因在RS中的作用强于PSP-P(优势比为13.2比4.5)。各临床亚组间的基因频率差异无统计学意义。载脂蛋白E基因分型无差异。PSP的经典临床描述包括核上性凝视麻痹、早衰和痴呆，但不能充分描述这一系列病理确诊病例中的三分之一。我们认为，PSP-P代表了第二种离散的临床表型，需要在临床上与经典的PSP(RS)区分开来。脑桥底部不同的tau异构体沉积表明，这可能最终被证明是一个离散的病因学实体。
The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups. In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson's syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson's disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P. The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes. The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.