Corriveau-Lecavalier Nick, Piura Yoav D, Appleby Brian S, Shir Dror, Barnard Leland R, Gogineni Venkatsampath, Jones David T, Day Gregory S
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
Ann Clin Transl Neurol. 2024 Dec;11(12):3227-3237. doi: 10.1002/acn3.52230. Epub 2024 Oct 29.
Prion disease classically presents with rapidly progressive dementia, leading to death within months of diagnosis. Advances in diagnostic testing have improved recognition of patients with atypical presentations and protracted disease courses, raising key questions surrounding the relationship between patterns of neurodegeneration and survival. We assessed the contribution of fluorodeoxyglucose (FDG-PET) imaging for this purpose.
FDG-PET were performed in 40 clinic patients with prion disease. FDG-PET images were projected onto latent factors generated in an external dataset to yield patient-specific eigenvalues. Eigenvalues were input into a clustering algorithm to generate data-driven clusters, which were compared by survival time.
Median age at FDG-PET was 65.3 years (range 23-85). Median time from FDG-PET to death was 3.7 months (range 0.3-19.0). Four data-driven clusters were generated, termed "Neocortical" (n = 7), "Transitional" (n = 12), "Temporo-parietal" (n = 13), and "Deep nuclei" (n = 6). Deep nuclei and transitional clusters had a shorter survival time than the neocortical cluster. Subsequent analyses suggested that this difference was driven by greater hypometabolism of deep nuclei relative to neocortical areas. FDG-PET-patterns were not associated with demographic (age and sex) or clinical (CSF total-tau, 14-3-3) variables.
Greater hypometabolism within deep nuclei relative to neocortical areas associated with more rapid decline in patients with prion disease and vice versa. FDG-PET informs large-scale network physiology and may inform the relationship between spreading pathology and survival in patients with prion disease. Future studies should consider whether FDG-PET may enrich multimodal prion disease prognostication models.
朊病毒病通常表现为快速进展性痴呆，在诊断后数月内导致死亡。诊断检测的进展提高了对非典型表现和病程迁延患者的识别，引发了关于神经退行性变模式与生存之间关系的关键问题。我们为此评估了氟脱氧葡萄糖（FDG-PET）成像的作用。
对40例临床诊断为朊病毒病的患者进行了FDG-PET检查。将FDG-PET图像投影到外部数据集中生成的潜在因子上，以产生患者特异性特征值。将特征值输入聚类算法以生成数据驱动的聚类，并按生存时间进行比较。
进行FDG-PET检查时的中位年龄为65.3岁（范围23-85岁）。从FDG-PET检查到死亡的中位时间为3.7个月（范围0.3-19.0个月）。生成了四个数据驱动的聚类，分别称为“新皮质”（n = 7）、“过渡型”（n = 12）、“颞顶叶”（n = 13）和“深部核团”（n = 6）。深部核团和过渡型聚类的生存时间比新皮质聚类短。后续分析表明，这种差异是由深部核团相对于新皮质区域更大程度的代谢减低所驱动。FDG-PET模式与人口统计学（年龄和性别）或临床（脑脊液总tau蛋白、14-3-3）变量无关。
与新皮质区域相比，深部核团内更大程度的代谢减低与朊病毒病患者更快的病情恶化相关，反之亦然。FDG-PET反映了大规模网络生理学情况，可能有助于了解朊病毒病患者病理传播与生存之间的关系。未来的研究应考虑FDG-PET是否可以丰富多模式朊病毒病预后模型。
