Giménez-Garzó Carla, Garcés Juan José, Urios Amparo, Mangas-Losada Alba, García-García Raquel, González-López Olga, Giner-Durán Remedios, Escudero-García Desamparados, Serra Miguel Angel, Soria Emilio, Felipo Vicente, Montoliu Carmina
Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain.
IDAL, Intelligent Data Analysis Laboratory, Escuela Técnica Superior de Ingeniería, Valencia, Spain.
PLoS One. 2017 Feb 1;12(2):e0171211. doi: 10.1371/journal.pone.0171211. eCollection 2017.
The psychometric hepatic encephalopathy score (PHES) is the "gold standard" for minimal hepatic encephalopathy (MHE) diagnosis. Some reports suggest that some cirrhotic patients "without" MHE according to PHES show neurological deficits and other reports that neurological alterations are not homogeneous in all cirrhotic patients. This work aimed to assess whether: 1) a relevant proportion of cirrhotic patients show neurological deficits not detected by PHES; 2) cirrhotic patients with mild neurological deficits are a homogeneous population or may be classified in sub-groups according to specific deficits.
Cirrhotic patients "without" (n = 56) or "with" MHE (n = 41) according to PHES and controls (n = 52) performed psychometric tests assessing attention, concentration, mental processing speed, working memory and bimanual and visuomotor coordination. Heterogeneity of neurological alterations was analysed using Hierarchical Clustering Analysis.
PHES classified as "with" MHE 42% of patients. Around 40% of patients "without" MHE according to PHES fail two psychometric tests. Oral SDMT, d2, bimanual and visuo-motor coordination tests are failed by 54, 51, 51 and 43% of patients, respectively. The earliest neurological alterations are different for different patients. Hierarchical clustering analysis shows that patients "without" MHE according to PHES may be classified in clusters according to the tests failed. In some patients coordination impairment appear before cognitive impairment while in others concentration and attention deficits appear before.
PHES is not sensitive enough to detect early neurological alterations in a relevant proportion of cirrhotic patients. Oral SDMT, d2 and bimanual and visuo-motor coordination tests are more sensitive. The earliest neurological alterations are different in different cirrhotic patients. These data also have relevant clinical implications. Patients classified as "without MHE" by PHES belonging to clusters 3 and 4 in our study have a high risk of suffering clinical complications, including overt HE and must be diagnosed and clinically followed.
心理测量肝性脑病评分(PHES)是诊断轻微肝性脑病(MHE)的“金标准”。一些报告表明,部分根据PHES诊断为“无”MHE的肝硬化患者存在神经功能缺损,还有报告称神经功能改变在所有肝硬化患者中并非均一。本研究旨在评估:1)相当比例的肝硬化患者是否存在PHES未检测到的神经功能缺损;2)有轻度神经功能缺损的肝硬化患者是否为同质人群,或是否可根据特定缺损分为亚组。
根据PHES诊断为“无”(n = 56)或“有”MHE(n = 41)的肝硬化患者以及对照组(n = 52)进行心理测量测试,以评估注意力、专注力、心理加工速度、工作记忆以及双手和视觉运动协调性。使用层次聚类分析来分析神经功能改变的异质性。
PHES将42%的患者分类为“有”MHE。约40%根据PHES诊断为“无”MHE的患者未能通过两项心理测量测试。分别有54%、51%、51%和43%的患者未能通过口头符号数字模式测试(SDMT)、d2测试、双手协调性测试和视觉运动协调性测试。不同患者最早出现的神经功能改变有所不同。层次聚类分析表明,根据PHES诊断为“无”MHE的患者可根据未通过的测试分为不同类别。在一些患者中,协调性损害先于认知损害出现,而在另一些患者中,专注力和注意力缺损先出现。
PHES在检测相当比例肝硬化患者早期神经功能改变方面不够敏感。口头SDMT、d2测试以及双手和视觉运动协调性测试更为敏感。不同肝硬化患者最早出现的神经功能改变各不相同。这些数据也具有重要的临床意义。在我们的研究中,根据PHES分类为“无MHE”且属于第3组和第4组的患者发生临床并发症(包括显性肝性脑病)的风险较高,必须进行诊断并接受临床随访。