Hellström Santtu, Sajanti Antti, Jhaveri Aditya, Srinath Abhinav, Bennett Carolyn, Cao Ying, Koskimäki Fredrika, Falter Johannes, Frantzén Janek, Lyne Seán B, Rantamäki Tomi, Takala Riikka, Posti Jussi P, Roine Susanna, Kolehmainen Sulo, Jänkälä Miro, Puolitaival Jukka, Girard Romuald, Rahi Melissa, Rinne Jaakko, Castrén Eero, Koskimäki Janne
Neurocenter, Department of Neurosurgery, Turku University Hospital and University of Turku, P.O. Box 52, FI-20521, Turku, Finland.
Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences, Chicago, IL, 60637, USA.
Brain Spine. 2024 Dec 24;5:104173. doi: 10.1016/j.bas.2024.104173. eCollection 2025.
Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is recognized as a diagnostic and prognostic blood biomarker for traumatic brain injury (TBI). This study aimed to evaluate whether UCH-L1 concentrations measured in patients' urine post-injury could serve as a diagnostic or prognostic biomarker for outcomes in various types of acute brain injuries (ABI).
This pilot study included 46 ABI patients: aneurysmal subarachnoid hemorrhage (n = 22), ischemic stroke (n = 16), and traumatic brain injury (n = 8), along with three healthy controls. Urine samples were collected at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) periods post-admission. UCH-L1 and creatinine levels were quantified using ELISA. UCH-L1 concentrations were compared to functional outcomes (modified Rankin Scale, mRS) and dichotomized into favorable (mRS 0-3) and unfavorable (mRS 4-6) groups. Non-parametric statistical tests and ROC analysis was performed.
UCH-L1 concentrations in healthy controls were significantly lower compared to both early and late samples after ABI (p ≤ 0.001). The diagnostic performance of urine UCH-L1 at early timepoint showed excellent discriminatory ability, with AUC of 97.6% (95% CI: 93.0-100, p = 0.006 (sensitivity 98%, specificity 100%). Urine UCH-L1 concentrations, both with and without creatinine normalization, did not distinguish between favorable and unfavorable outcomes in either early (p = 0.88 and p = 0.36) or late samples (p = 0.98 and p = 0.30) in any types of ABI.
Although UCH-L1 concentrations in urine did not differentiate between favorable and unfavorable outcomes, a significant difference was observed between healthy subjects and ABI patients. This finding underscores the significant diagnostic utility of urine UCH-L1 concentrations, regardless of the type of acute brain injury.
泛素羧基末端水解酶L1（UCH-L1）被认为是创伤性脑损伤（TBI）的一种诊断和预后血液生物标志物。本研究旨在评估损伤后患者尿液中检测到的UCH-L1浓度是否可作为各种类型急性脑损伤（ABI）预后的诊断或预后生物标志物。
这项初步研究纳入了46例ABI患者，包括动脉瘤性蛛网膜下腔出血（n = 22）、缺血性中风（n = 16）和创伤性脑损伤（n = 8），以及三名健康对照者。在入院后的早期（1.50 ± 0.70天）和晚期（9.17 ± 3.40天）收集尿液样本。使用酶联免疫吸附测定法（ELISA）对UCH-L1和肌酐水平进行定量。将UCH-L1浓度与功能结局（改良Rankin量表，mRS）进行比较，并分为良好（mRS 0 - 3）和不良（mRS 4 - 6）组。进行非参数统计检验和ROC分析。
与ABI后的早期和晚期样本相比，健康对照者的UCH-L1浓度显著较低（p≤0.001）。尿液UCH-L1在早期时间点的诊断性能显示出优异的鉴别能力，曲线下面积（AUC）为97.6%（95%置信区间：93.0 - 100，p = 0.006（敏感性98%，特异性100%））。在任何类型的ABI中，无论是否进行肌酐标准化，尿液UCH-L1浓度在早期（p = 0.88和p = 0.36）或晚期样本（p = 0.98和p = 0.30）中均无法区分良好和不良结局。
尽管尿液中的UCH-L1浓度无法区分良好和不良结局，但在健康受试者和ABI患者之间观察到了显著差异。这一发现强调了尿液UCH-L1浓度的显著诊断效用，无论急性脑损伤的类型如何。
