Antonini A, Leenders K L, Spiegel R, Meier D, Vontobel P, Weigell-Weber M, Sanchez-Pernaute R, de Yébenez J G, Boesiger P, Weindl A, Maguire R P
PET Department, Paul Scherrer Institute, Villigen, Switzerland.
Brain. 1996 Dec;119 ( Pt 6):2085-95. doi: 10.1093/brain/119.6.2085.
We used PET scans with the tracers [18F]fluorodeoxyglucose (FDG) and [11C]raclopride (RACLO) to study glucose metabolism and dopamine D2 receptor binding in the caudate nucleus and putamen of 18 carriers of the Huntington's disease gene mutation (10 asymptomatic subjects and eight untreated symptomatic Huntington's disease patients in an early disease stage). We also performed MRI scans and measured the bicaudate ratio (BCR) in the same subjects. Data were compared with those from nine mutation-negative members of Huntington's disease families and separate groups of age matched controls. The PET scans were repeated 1.5-3 years later in six of the asymptomatic gene carriers. Symptomatic Huntington's disease patients showed a marked reduction of FDG and RACLO uptake in the caudate nucleus and putamen and a significant increase of BCR. Asymptomatic mutation carriers revealed significant hypometabolism in the caudate nucleus and putamen. The RACLO binding was significantly decreased in the putamen. Decrements of caudate nucleus tracer uptake, particularly RACLO, correlated significantly with BCR increases in both symptomatic and asymptomatic gene carriers. In asymptomatic carriers, metabolic and receptor binding decreases were also significantly associated with the CAG repeat number but not with the individual's age. Discriminant function analysis correctly classified clinical and genetic status in 24 of 27 subjects on the basis of their striatal PET values (83% sensitivity and 100% specificity). Three asymptomatic mutation carriers were classified/grouped together with mutation-negative subjects, indicating that these individuals had normal striatal RACLO and FDG uptake. Follow-up PET data from gene-positive subjects showed a significant reduction in the mean striatal RACLO binding of 6.3% per year. Striatal glucose metabolism revealed an overall non significant 2.3% decrease per year. These data indicate that asymptomatic Huntington's disease mutation carriers may show normal neuronal function for a long period of life. These findings also suggest that it may be possible to predict when an asymptomatic gene carrier will develop clinical symptoms from serial PET measurements of striatal function.
我们使用正电子发射断层扫描（PET）以及示踪剂[18F]氟脱氧葡萄糖（FDG）和[11C]雷氯必利（RACLO），来研究18名亨廷顿舞蹈症基因突变携带者（10名无症状受试者和8名早期未治疗的有症状亨廷顿舞蹈症患者）尾状核和壳核中的葡萄糖代谢及多巴胺D2受体结合情况。我们还对这些受试者进行了磁共振成像（MRI）扫描，并测量了双侧尾状核比率（BCR）。将数据与9名亨廷顿舞蹈症家族中未携带突变的成员以及年龄匹配的对照组数据进行比较。6名无症状基因携带者在1.5至3年后再次进行了PET扫描。有症状的亨廷顿舞蹈症患者尾状核和壳核中FDG和RACLO摄取显著减少，BCR显著增加。无症状突变携带者尾状核和壳核显示出明显的代谢减退。壳核中RACLO结合显著降低。在有症状和无症状基因携带者中，尾状核示踪剂摄取的减少，尤其是RACLO，与BCR增加显著相关。在无症状携带者中，代谢和受体结合减少也与CAG重复序列数量显著相关，但与个体年龄无关。判别函数分析基于纹状体PET值在27名受试者中的24名中正确分类了临床和基因状态（敏感性83%，特异性100%）。3名无症状突变携带者与未携带突变的受试者归为一组，表明这些个体纹状体RACLO和FDG摄取正常。基因阳性受试者的随访PET数据显示，纹状体RACLO平均结合每年显著降低6.3%。纹状体葡萄糖代谢每年总体下降2.3%，无显著意义。这些数据表明，无症状的亨廷顿舞蹈症突变携带者在很长一段时间内可能表现出正常的神经元功能。这些发现还表明，通过对纹状体功能进行系列PET测量，有可能预测无症状基因携带者何时会出现临床症状。
