Department of Neurology, University Medical Center Ljubljana, Zaloška cesta 2a, 1000 Ljubljana, Slovenia.
Institute of Pathology, Medical Faculty, University of Ljubljana, Korytkova ulica 2, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2023 Aug 23;24(17):13081. doi: 10.3390/ijms241713081.
The co-occurrence of multiple proteinopathies is being increasingly recognized in neurodegenerative disorders and poses a challenge in differential diagnosis and patient selection for clinical trials. Changes in brain metabolism captured by positron emission tomography (PET) with F-fluorodeoxyglucose (FDG) allow us to differentiate between different neurodegenerative disorders either by visual exploration or by studying disease-specific metabolic networks in individual patients. However, the impact of multiple proteinopathies on brain metabolism and metabolic networks remains unknown due to the absence of pathological studies. In this case study, we present a 67-year-old patient with rapidly progressing dementia clinically diagnosed with probable sporadic Creutzfeldt-Jakob disease (sCJD). However, in addition to the expected pronounced cortical and subcortical hypometabolism characteristic of sCJD, the brain FDG PET revealed an intriguing finding of unexpected relative hypermetabolism in the bilateral putamina, raising suspicions of coexisting Parkinson's disease (PD). Additional investigation of disease-specific metabolic brain networks revealed elevated expression of both CJD-related pattern (CJDRP) and PD-related pattern (PDRP) networks. The patient eventually developed akinetic mutism and passed away seven weeks after symptom onset. Neuropathological examination confirmed neuropathological changes consistent with sCJD and the presence of Lewy bodies confirming PD pathology. Additionally, hyperphosphorylated tau and TDP-43 pathology were observed, a combination of four proteinopathies that had not been previously reported. Overall, this case provides valuable insights into the complex interplay of neurodegenerative pathologies and their impact on metabolic brain changes, emphasizing the role of metabolic brain imaging in evaluating potential presence of multiple proteinopathies.
多种蛋白病的共存在神经退行性疾病中越来越被认识到，这给鉴别诊断和临床试验患者选择带来了挑战。正电子发射断层扫描（PET）用 F-氟脱氧葡萄糖（FDG）检测到的脑代谢变化使我们能够通过视觉探索或研究个体患者的特定疾病代谢网络来区分不同的神经退行性疾病。然而，由于缺乏病理研究，多种蛋白病对脑代谢和代谢网络的影响仍然未知。在这个病例研究中，我们介绍了一位 67 岁的患者，他患有快速进展的痴呆症，临床上被诊断为可能的散发性克雅氏病（sCJD）。然而，除了预期的 sCJD 特征性明显的皮质和皮质下代谢低下外，大脑 FDG PET 还显示出双侧壳核令人惊讶的相对代谢亢进，这让人怀疑同时存在帕金森病（PD）。对特定疾病代谢脑网络的进一步研究显示，CJD 相关模式（CJDRP）和 PD 相关模式（PDRP）网络的表达均升高。患者最终发展为无动性缄默症，并在症状出现后七周去世。神经病理学检查证实了符合 sCJD 的神经病理学变化，以及Lewy 体的存在，证实了 PD 病理学。此外，还观察到过度磷酸化的 tau 和 TDP-43 病理学，这是四种以前未报道过的蛋白病的组合。总的来说，这个病例为神经退行性病变的复杂相互作用及其对代谢性脑变化的影响提供了有价值的见解，强调了代谢性脑成像在评估潜在的多种蛋白病存在方面的作用。
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