Vita-Salute San Raffaele University, Milan, Italy; IRCCS San Raffaele Scientific Institute, Milan, Italy; Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Division of Neurorehabilitation, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland.
Neuroimage Clin. 2024;42:103592. doi: 10.1016/j.nicl.2024.103592. Epub 2024 Mar 14.
A proportion of patients clinically diagnosed with Parkinson's disease (PD) can have a I-FP-CIT-SPECT scan without evidence of dopaminergic deficit (SWEDD), generating a debate about the underlying biological mechanisms. This study investigated differences in clinical features, I-FP-CIT binding, molecular connectivity, as well as clinical and imaging progression between SWEDD and PD patients. We included 36 SWEDD, 49 de novo idiopathic PD, and 49 healthy controls with I-FP-CIT-SPECT from the Parkinson's Progression Markers Initiative. Clinical and imaging 2-year follow-ups were available for 27 SWEDD and 40 PD. Regional-based and voxel-wise analysis assessed dopaminergic integrity in dorsal and ventral striatal, as well as extrastriatal regions, at baseline and follow-up. Molecular connectivity analyses evaluated dopaminergic pathways. Spatial correlation analyses tested whether I-FP-CIT-binding alterations would also pertain to the serotoninergic system. SWEDD and PD patients showed comparable symptoms at baseline, except for hyposmia, which was more severe for PD. PD showed significantly lower striatal and extrastriatal I-FP-CIT-binding compared to SWEDD and controls. SWEDD exhibited lower binding than controls in striatal regions, insula, and olfactory cortex. Both PD and SWEDD showed extensive altered connectivity of dopaminergic pathways, however, with major impairment in the mesocorticolimbic system for SWEDD. Motor symptoms and dopaminergic deficits worsened after 2 years for PD only. The limited dopaminergic impairment and its stability over time observed for SWEDD, as well as the presence of extrastriatal I-FP-CIT binding alterations and prevalent mesocorticolimbic connectivity impairment, suggest other mechanisms contributing to SWEDD pathophysiology.
一部分临床诊断为帕金森病（PD）的患者可能存在多巴胺能缺陷（SWEDD）的 I-FP-CIT-SPECT 扫描无证据，这引发了对潜在生物学机制的争论。本研究调查了 SWEDD 和 PD 患者之间在临床特征、I-FP-CIT 结合、分子连接以及临床和影像学进展方面的差异。我们纳入了来自帕金森进展标志物倡议的 36 例 SWEDD、49 例新诊断的特发性 PD 和 49 例健康对照者，进行了 I-FP-CIT-SPECT 扫描。SWEDD 中有 27 例和 PD 中有 40 例可获得 2 年的临床和影像学随访。基于区域和体素分析评估了背侧和腹侧纹状体以及纹状体外区域在基线和随访时的多巴胺能完整性。分子连接分析评估了多巴胺能通路。空间相关性分析测试了 I-FP-CIT 结合改变是否也与 5-羟色胺能系统有关。SWEDD 和 PD 患者在基线时的症状相似，但 PD 患者的嗅觉障碍更为严重。与 SWEDD 和对照组相比，PD 患者的纹状体和纹状体外区域的 I-FP-CIT 结合明显更低。SWEDD 患者的纹状体区域、岛叶和嗅觉皮层的结合低于对照组。PD 和 SWEDD 患者的多巴胺能通路连接都广泛改变，但 SWEDD 患者的中皮质边缘系统受损更严重。只有 PD 患者的运动症状和多巴胺能缺陷在 2 年后恶化。SWEDD 患者的多巴胺能损伤有限且随时间稳定，以及存在纹状体外 I-FP-CIT 结合改变和普遍存在的中皮质边缘系统连接损伤，表明 SWEDD 病理生理学可能存在其他机制。
