Gearing Marla, Juncos Jorge L, Procaccio Vincent, Gutekunst Claire-Anne, Marino-Rodriguez Elaine M, Gyure Kymberly A, Ono Shoichiro, Santoianni Robert, Krawiecki Nicolas S, Wallace Douglas C, Wainer Bruce H
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
Ann Neurol. 2002 Oct;52(4):465-76. doi: 10.1002/ana.10319.
The neuropathology of the primary dystonias is not well understood. We examined brains from identical twins with DYT1-negative, dopa-unresponsive dystonia. The twins exhibited mild developmental delays until age 12 years when they began developing rapidly progressive generalized dystonia. Genetic, metabolic, and imaging studies ruled out known causes of dystonia. Cognition was subnormal but stable until the last few years. Death occurred at ages 21 and 22 years. The brains were macroscopically unremarkable. Microscopic examination showed unusual glial fibrillary acidic protein-immunoreactive astrocytes in multiple regions and iron accumulation in pallidal and nigral neurons. However, the most striking findings were 1) eosinophilic, rod-like cytoplasmic inclusions in neocortical and thalamic neurons that were actin depolymerizing factor/cofilin-immunoreactive but only rarely actin-positive; and 2) abundant eosinophilic spherical structures in the striatum that were strongly actin- and actin depolymerizing factor/cofilin-positive. Electron microscopy suggested that these structures represent degenerating neurons and processes; the accumulating filaments had the same dimensions as actin microfilaments. To our knowledge, aggregation of actin has not been reported previously as the predominant feature in any neurodegenerative disease. Thus, our findings may shed light on a novel neuropathological change associated with dystonia that may represent a new degenerative mechanism involving actin, a ubiquitous constituent of the cytoskeletal system.
原发性肌张力障碍的神经病理学尚未完全明了。我们检查了患有DYT1阴性、对多巴无反应性肌张力障碍的同卵双胞胎的大脑。这对双胞胎在12岁之前表现出轻度发育迟缓，之后开始出现快速进展的全身性肌张力障碍。基因、代谢和影像学研究排除了已知的肌张力障碍病因。认知功能在过去几年之前一直低于正常水平但保持稳定。两人分别于21岁和22岁死亡。大脑在宏观上无明显异常。显微镜检查显示多个区域存在异常的胶质纤维酸性蛋白免疫反应性星形胶质细胞，苍白球和黑质神经元中有铁沉积。然而，最显著的发现是：1）新皮质和丘脑神经元中存在嗜酸性、棒状胞质包涵体，这些包涵体对肌动蛋白解聚因子/丝切蛋白呈免疫反应，但很少呈肌动蛋白阳性；2）纹状体中有大量嗜酸性球形结构，对肌动蛋白和肌动蛋白解聚因子/丝切蛋白呈强阳性。电子显微镜检查表明，这些结构代表正在退化的神经元和突起；积累的细丝与肌动蛋白微丝尺寸相同。据我们所知，肌动蛋白聚集此前尚未作为任何神经退行性疾病的主要特征被报道过。因此，我们的发现可能有助于揭示与肌张力障碍相关的一种新的神经病理学变化，这可能代表一种涉及肌动蛋白的新的退化机制，肌动蛋白是细胞骨架系统中普遍存在的成分。
