A reliability study of colour-Doppler sonography for the diagnosis of chronic cerebrospinal venous insufficiency shows low inter-rater agreement

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) has been extremely variable associated with multiple sclerosis in color-Doppler sonographic studies. We aimed to evaluate inter-rater agreement in color doppler sonograpy venous examination. Design: Inter-rater agreement study. Setting: First-referral multiple sclerosis centre. Participants: thirty-eight multiple sclerosis patients, and 55 age-matched (± 5 years) controls. Intervention: sonography was carried out in accordance with Zamboni's five criteria by 8 sonographers with different expertise, blinded to the status of cases and controls. Each subject was evaluated by two operators. Primary and secondary outcome measures: inter-rater agreement was measured through the Kappa statistics and the Intraclass Correlation Coefficient. Results: The agreement was no higher than chance for criterion 2-reflux in the deep cerebral veins (Kappa=-0.02) and 4-flow not Doppler-detectable in one or both the internal jugular (IJVs) or vertebral veins (VVs) (-0.09). It was substantially low for criterion 1-reflux in the IJVs and/or VVs (0.29), criterion 3-IJV stenosis or malformations (0.23), and criterion 5-absence of IJV diameter increase when passing from sitting to supine position (0.22). The Kappa value for CCSVI as a whole was 0.20 (95% confidence limits=-0.01 - 0.42). Intraclass Correlation Coefficients for the measure of cross-sectional area ranged from 0.05 to 0.25. Inter-rater agreement was low for CCSVI experts (kappa= 0.24; -0.11 to 0.59), and non-experts (0.20; -0.33 to 0.73); neurologists (0.21; -0.06 to 0.47) and non neurologists (0.18; -0.20 to 0.56); cases (0.19; -0.14 to 0.52) and controls (0.21; -0.08 to 0.49). Zamboni-trained neurosonographers ascertained CCSVI more frequently than non-trained. Conclusions: Agreement was unsatisfactory for the diagnosis of CCSVI as a whole, for each of its five criteria, and according to different subgroups. Standardization of the method is urgently needed prior to its further application in studies of patients with multiple sclerosis or other neurological diseases.

研究目的：慢性脑脊液静脉功能不全（Chronic cerebrospinal venous insufficiency, CCSVI）在彩色多普勒超声（color-Doppler sonographic）研究中与多发性硬化的关联表现极不稳定。本研究旨在评估彩色多普勒静脉超声检查中的观察者间一致性。研究设计：观察者间一致性研究。研究场所：首诊多发性硬化中心。研究对象：38名多发性硬化患者，以及55名年龄匹配（±5岁）的对照个体。检查实施：由8名不同专业背景的超声医师按照赞邦尼（Zamboni）提出的五项标准开展超声检查，所有医师对研究对象的分组情况设盲。每名受试者均由两名操作医师完成评估。主要与次要结局指标：通过Kappa统计量（Kappa statistics）与组内相关系数（Intraclass Correlation Coefficient, ICC）评估观察者间一致性。结果：针对第2项标准——大脑深静脉反流（Kappa=-0.02），以及第4项标准——单侧或双侧颈内静脉（internal jugular veins, IJVs）或椎静脉（vertebral veins, VVs）无法通过多普勒检测到血流（Kappa=-0.09），其观察者间一致性未优于随机水平。对于第1项标准——颈内静脉和/或椎静脉反流（Kappa=0.29）、第3项标准——颈内静脉狭窄或畸形（Kappa=0.23），以及第5项标准——从坐位转为平卧位时颈内静脉直径无增加（Kappa=0.22），其一致性均处于较低水平。CCSVI整体诊断的Kappa值为0.20（95%置信区间：-0.01~0.42）。横截面面积测量的组内相关系数范围为0.05~0.25。按亚组分析，CCSVI专家组（Kappa=0.24；95%CI：-0.11~0.59）、非专家组（Kappa=0.20；95%CI：-0.33~0.73）、神经科医师组（Kappa=0.21；95%CI：-0.06~0.47）、非神经科医师组（Kappa=0.18；95%CI：-0.20~0.56）、患者组（Kappa=0.19；95%CI：-0.14~0.52）以及对照组（Kappa=0.21；95%CI：-0.08~0.49）的观察者间一致性均较低。接受过赞邦尼方法培训的神经超声医师，相较于未接受培训者，更易确诊CCSVI。结论：无论是CCSVI的整体诊断，还是其五项单项标准，抑或是不同亚组的分析结果，其观察者间一致性均未达满意标准。在将该方法进一步应用于多发性硬化或其他神经系统疾病患者的研究之前，亟需对其操作流程进行标准化规范。