Singleton Amanda, Gwinn-Hardy Katrina, Sharabi Yehonotan, Li Sheng-Ting, Holmes Courtney, Dendi Raghuveer, Hardy John, Singleton Andrew, Crawley Anthony, Goldstein David S
Parkinson's Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Brain. 2004 Apr;127(Pt 4):768-72. doi: 10.1093/brain/awh081. Epub 2004 Jan 21.
Parkinson's disease patients frequently have symptoms and signs of autonomic nervous dysfunction that are the source of considerable disability. Recent studies have revealed that most patients with Parkinson's disease, and all with Parkinson's disease-associated orthostatic hypotension, have a loss of cardiac sympathetic innervation. Familial Parkinson's disease, caused by mutation of the gene encoding alpha-synuclein, also features orthostatic hypotension, sympathetic neurocirculatory failure and cardiac sympathetic denervation. We have recently described a whole-gene triplication of alpha-synuclein causing Lewy body parkinsonism in a large, well characterized family called the 'Iowa kindred'. Here we report the results of cardiac PET scanning using the sympathoneural imaging agent, 6-[18F]fluorodopamine in affected and unaffected members of this kindred. Four family members were studied, two with parkinsonism, one clinically normal and one with benign essential tremor alone. Both affected members had obvious loss of cardiac sympathetic innervation; the unaffected member had normal innervation, as did the member with isolated essential tremor. The results indicate that, in this family, where disease is caused by overexpression of normal alpha-synuclein, cardiac sympathetic denervation cosegregates with parkinsonism. Post-mortem studies have demonstrated synuclein-positive Lewy body formation in the brains of individuals with parkinsonism who were also in the family described here and who also carry this triplication. These results indicate that both parkinsonism and cardiac sympathetic denervation can result from an excess of normal synuclein.
帕金森病患者常常出现自主神经功能障碍的症状和体征，这些症状和体征是导致严重残疾的根源。最近的研究表明，大多数帕金森病患者，以及所有患有帕金森病相关体位性低血压的患者，都存在心脏交感神经支配缺失的情况。由编码α-突触核蛋白的基因突变引起的家族性帕金森病，也具有体位性低血压、交感神经循环衰竭和心脏交感神经去神经支配的特征。我们最近在一个名为“Iowa家族”的大型、特征明确的家族中描述了α-突触核蛋白的全基因三倍体导致路易体帕金森病。在此，我们报告了使用交感神经成像剂6-[18F]氟多巴胺对该家族中患病和未患病成员进行心脏PET扫描的结果。研究了四名家族成员，两名患有帕金森病，一名临床正常，一名仅患有良性特发性震颤。两名患病成员均有明显的心脏交感神经支配缺失；未患病成员的神经支配正常，仅患有特发性震颤的成员也是如此。结果表明，在这个由正常α-突触核蛋白过度表达导致疾病的家族中，心脏交感神经去神经支配与帕金森病共分离。尸检研究表明，在此描述的家族中患有帕金森病且携带这种三倍体的个体大脑中存在突触核蛋白阳性路易体形成。这些结果表明，帕金森病和心脏交感神经去神经支配都可能由正常突触核蛋白过量引起。
