Gusev E I, Blokhin V E, Vartanov S A, Martynov M Yu, Katunina E A, Alesenko A V, Denisova I A, Pavlova E N, Polterovich V M, Kucheryanu V G, Shupik M A, Nodel M R, Kalinkin A L, Sokolov S A, Chubarova T V, Shakleina M V, Pronina T S, Ugryumov M V
Pirogov Russian National Research Medical University, Moscow, Russia.
Koltsov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2021;121(1):9-20. doi: 10.17116/jnevro20211210119.
The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility» analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.
本文总结了关于帕金森病(PD)早期(临床前)诊断发展的文献及作者的数据。实施这种诊断将促进预防性治疗的应用,并改变对患者诊断和治疗的投入。本文宣称,目前PD早期诊断的唯一方法是黑质纹状体多巴胺能系统的正电子发射断层扫描,但由于成本高昂,它不能用于预防性检查。作者认为,一种特异性较低但更有前景的PD早期诊断发展方法是在PD前驱期患者的体液(主要是血液)中寻找标志物。事实上,根据特征性运动前症状,在被选入PD前驱期风险组的患者中发现了许多标志物,如单胺、鞘脂、尿酸盐代谢物水平的变化以及氧化应激指标。此外,据推测,只有在临床前早期阶段的PD动物模型中才有可能在更早的前驱前期阶段寻找血液标志物。这种方法也可用于验证在PD临床阶段患者中鉴定出的血液标志物。同样明显的是,影响PD发病率的复杂社会经济因素在发达国家和发展中国家有所不同。帕金森病的社会和医疗成本巨大,努力改善PD的临床前早期诊断将带来可观的经济和社会效益。例如,这将允许有效地选择患者进行临床前诊断测试。为了在考虑社会经济问题不确定性的情况下评估该策略的有效性,提出了对“成本效用”分析的修改。首次开发并研究了一个包括临床前诊断测试和可能的神经保护治疗的PD马尔可夫模型。这一过程的分析结果表明,从社会经济角度来看,开发一种新的多模式策略的想法很有前景。