Wszolek Z K, Pfeiffer R F, Bhatt M H, Schelper R L, Cordes M, Snow B J, Rodnitzky R L, Wolters E C, Arwert F, Calne D B
Section of Neurology, University of Nebraska Medical Center, Omaha 68198-2045.
Ann Neurol. 1992 Sep;32(3):312-20. doi: 10.1002/ana.410320303.
We describe a family with nearly 300 members over 8 generations with 32 affected individuals who have an autosomal dominant neurodegenerative disease characterized by progressive parkinsonism with dystonia unrelated to medications, dementia, ocular motility abnormalities, pyramidal tract dysfunction, frontal lobe release signs, perseverative vocalizations, and urinary incontinence. The course is exceptionally aggressive; symptom onset and death consistently occur in the fifth decade. Positron emission tomographic studies with [18F]6-fluoro-L-dopa (6FD) were performed in 4 patients and 7 individuals at risk for development of the disease. All affected subjects had markedly reduced striatal uptake of 6FD (p less than 0.001). All individuals at risk had normal striatal uptake, but high 6FD uptake rate constants were noted in 3 of the 7 studied. Autopsy findings revealed severe neuronal loss with gliosis in substantia nigra, pontine tegmentum, and globus pallidus, with less involvement of the caudate and the putamen. There were no plaques, tangles, Lewy bodies, or amyloid bodies. This kindred appears to represent a neurodegenerative disease not heretofore described. We propose the following name for this new genetic disease: autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration.
我们描述了一个家族，该家族历经8代，有近300名成员，其中32名患者患有一种常染色体显性神经退行性疾病，其特征为进行性帕金森症伴肌张力障碍（与药物无关）、痴呆、眼球运动异常、锥体束功能障碍、额叶释放征、持续性发声和尿失禁。病程异常凶险；症状通常在第五个十年出现并导致死亡。对4例患者和7例有患病风险的个体进行了[18F]6-氟-L-多巴（6FD）正电子发射断层扫描研究。所有患病个体的纹状体对6FD的摄取均显著降低（p<0.001）。所有有患病风险的个体纹状体摄取均正常，但在7例研究对象中有3例的6FD摄取速率常数较高。尸检结果显示黑质、脑桥被盖和苍白球有严重的神经元丢失伴胶质增生，尾状核和壳核受累较轻。没有斑块、缠结、路易小体或淀粉样体。这个家族似乎代表了一种此前未被描述过的神经退行性疾病。我们为这种新的遗传病提出以下命名：常染色体显性帕金森症和痴呆伴苍白球-脑桥-黑质变性。
