Purpose

Scans without evidence of dopaminergic deficit (SWEDD) have been initially described in a minority of subjects with suspected Parkinson’s disease (PD). Although a highly controversial entity, longitudinal studies showed that SWEDD cases mostly involve non-degenerative conditions mimicking PD or misattribution of scan images to normal status. Using the Parkinson’s Progression Markers Initiative (PPMI) cohort, we undertook a case-controlled analysis of [123I]N-ω-fluoropropyl-2β-carbomethoxy-iodophenyl nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT) images to measure extrastriatal serotonergic transporter (SERT) density in SWEDD and PD.

Procedures

We included 37 SWEDD cases (mean age 60 years, 33 % female) with available [123I]FP-CIT SPECT imaging and high-resolution T1-weighted magnetic resonance imaging (MRI) for coregistration. Sixty-one controls and 62 similarly aged PD subjects were included for group comparisons. Regional [123I]FP-CIT was extracted with PETPVE12 using geometric transfer matrix and partial volume effect correction.

Results

PD subjects showed significantly lower [123I]FP-CIT binding in both striatal (caudate nucleus and putamen) and extrastriatal regions (pallidum and insula) compared with controls and SWEDD (all between-group p < 0.0001). PD group also showed lower binding in the thalamus relative to controls (p = 0.007). Receiver operating characteristics (ROC) area under the curve (AUC) did not show a significant difference when using extrastriatal region in addition to striatal ROIs for the separation of SWEDD and PD (95 % ROC-AUC for both methods, p = 0.52). In addition, striatal [123I]FP-CIT binding contralateral to the clinically more affected side was usually lower for PD (> 75 %) but not for SWEDD (< 49 %, p < 0.002). No significant difference regarding [123I]FP-CIT binding was observed between SWEDD and controls.

Conclusion

These findings corroborate the view that SWEDD cases represent a heterogeneous group of conditions not involving dopaminergic and serotonergic terminals. Further studies are warranted to be assessed whether using extrastriatal [123I]FP-CIT evaluation can be of help in the assessment of degenerative parkinsonism.

中文翻译：

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扫描中保留的纹状体外 123I-FP-CIT 结合没有多巴胺能缺陷 (SWEDD) 的证据。

目的

最初在少数疑似帕金森病 (PD) 的受试者中描述了没有多巴胺能缺陷 (SWEDD) 证据的扫描。尽管是一个极具争议的实体，但纵向研究表明，SWEDD 病例大多涉及模仿 PD 的非退行性病症或将扫描图像错误归因于正常状态。使用帕金森病进展标志物倡议 (PPMI) 队列，我们​​对 [123I]N-ω-氟丙基-2β-碳甲氧基-碘苯基去甲托烷 ([123I]FP-CIT) 单光子发射计算机断层扫描 (SPECT) 进行了病例对照分析用于测量 SWEDD 和 PD 中纹状体外血清素转运蛋白 (SERT) 密度的图像。

程序

我们纳入了 37 例 SWEDD 病例（平均年龄 60 岁，33% 为女性），可用 [123I]FP-CIT SPECT 成像和高分辨率 T1 加权磁共振成像 (MRI) 进行配准。包括 61 名对照和 62 名年龄相仿的 PD 受试者进行组比较。区域[123I]FP-CIT 使用PETPVE12 提取，使用几何传递矩阵和部分体积效应校正。

结果

与对照组和 SWEDD 相比，PD 受试者在纹状体（尾状核和壳核）和纹状体外区域（苍白球和脑岛）中的 [123I]FP-CIT 结合显着降低（所有组间p  < 0.0001）。与对照组相比，PD 组还显示出较低的丘脑结合（p  = 0.007）。除了纹状体 ROI 外，当使用纹状体外区域分离 SWEDD 和 PD 时，接受者操作特征 (ROC) 曲线下面积 (AUC) 没有显示显着差异（两种方法的 ROC-AUC 均为 95%，p  = 0.52）。此外，对于 PD (> 75 %) 而言，纹状体 [123I]FP-CIT 结合对侧临床上受影响较大的一侧通常较低，但对于 SWEDD（< 49 %，p < 0.002)。在 SWEDD 和对照之间没有观察到关于 [123I]FP-CIT 结合的显着差异。

结论

这些发现证实了 SWEDD 病例代表一组不涉及多巴胺能和 5-羟色胺能终端的异质性疾病的观点。需要进一步研究评估使用纹外 [123I]FP-CIT 评估是否有助于评估退行性帕金森病。