Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR 5287, Université de Bordeaux, 33076, Bordeaux, France.
J Neurol. 2022 Sep;269(9):4909-4919. doi: 10.1007/s00415-022-11135-6. Epub 2022 May 3.
The understanding of fatal familial insomnia (FFI), a rare neurodegenerative autosomal dominant prion disease, has improved in recent years as more cases were reported. This work aimed to propose new diagnostic criteria for FFI with optimal sensitivity, specificity, and likelihood ratio.
An international group of experts was established and 128 genetically confirmed FFI cases and 281 non-FFI prion disease controls are enrolled in the validation process. The new criteria were proposed based on the following steps with two-round expert consultation: (1) Validation of the 2018 FFI criteria. (2) Diagnostic item selection according to statistical analysis and expert consensus. (3) Validation of the new criteria.
The 2018 criteria for possible FFI had a sensitivity of 90.6%, a specificity of 83.3%, with a positive likelihood ratio (PLR) of 5.43, and a negative likelihood ratio (NLR) of 0.11; and the probable FFI criteria had a sensitivity of 83.6%, specificity of 92.9%, with a PLR of 11.77, and a NLR of 0.18. The new criteria included more specific and/or common clinical features, two exclusion items, and summarized a precise and flexible diagnostic hierarchy. The new criteria for possible FFI had therefore reached a better sensitivity and specificity (92.2% and 96.1%, respectively), a PLR of 23.64 and a NLR of 0.08, whereas the probable FFI criteria showed a sensitivity of 90.6%, a specificity of 98.2%, with a PLR of 50.33 and a NLR of 0.095.
We propose new clinical diagnostic criteria for FFI, for a better refining of the clinical hallmarks of the disease that ultimately would help an early recognition of FFI and a better differentiation from other prion diseases.
随着更多病例的报道，人们对致命家族性失眠症（FFI）这种罕见的神经退行性常染色体显性朊病毒病的认识近年来有所提高。本研究旨在提出新的诊断标准，以获得最佳的灵敏度、特异性和似然比。
成立了一个国际专家组，纳入了 128 例基因确诊的 FFI 病例和 281 例非 FFI 朊病毒病对照进行验证。新的标准是通过以下两步两轮专家咨询提出的：（1）验证 2018 年 FFI 标准。（2）根据统计分析和专家共识选择诊断项目。（3）验证新的标准。
可能的 FFI 的 2018 年标准的灵敏度为 90.6%，特异性为 83.3%，阳性似然比（PLR）为 5.43，阴性似然比（NLR）为 0.11；可能的 FFI 的标准的灵敏度为 83.6%，特异性为 92.9%，阳性似然比为 11.77，阴性似然比为 0.18。新的标准纳入了更具体和/或常见的临床特征、两个排除项目，并总结了一个精确和灵活的诊断层次结构。可能的 FFI 的新标准因此达到了更好的灵敏度和特异性（分别为 92.2%和 96.1%），阳性似然比为 23.64，阴性似然比为 0.08，而可能的 FFI 的标准显示出 90.6%的灵敏度，98.2%的特异性，阳性似然比为 50.33，阴性似然比为 0.095。
我们提出了新的 FFI 临床诊断标准，以更好地细化疾病的临床特征，最终有助于早期识别 FFI 并更好地区分其他朊病毒病。
