Kiiski Heikki, Tenhunen Jyrki, Ala-Peijari Marika, Huhtala Heini, Hämäläinen Mari, Långsjö Jaakko, Moilanen Eeva, Narkilahti Susanna, Öhman Juha, Peltola Jukka
Critical Care Medicine Research Group, Department of Intensive Care, Tampere University Hospital, Tampere, Finland; NeuroGroup, BioMediTech, University of Tampere, Tampere, Finland.
Critical Care Medicine Research Group, Department of Intensive Care, Tampere University Hospital, Tampere, Finland; Department of Surgical Sciences, Division of Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
J Neurol Sci. 2016 Feb 15;361:144-9. doi: 10.1016/j.jns.2015.12.046. Epub 2015 Dec 29.
Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of long-term disability and death. After primary hemorrhage, secondary brain injury is the main cause of mortality and morbidity. Despite extensive research, reliable prognostic biomarkers are lacking. We measured ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) levels in aSAH patients to evaluate its prognostic potential. This is the first time that plasma UCH-L1 has been studied as a potential prognostic biomarker in patients with aSAH.
In this prospective population-based study, UCH-L1 levels were measured in aSAH patients (n=47) for up to five days. UCH-L1 was measured at 0, 12 and 24h after the admission to the intensive care unit (ICU) and daily thereafter until the patient was transferred from the ICU. Only patients whose UCH-L1 was measured within 24h from aSAH were included in the study. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at six months after aSAH.
UCH-L1 levels during the first 24h after aSAH were not significantly different between the groups with favorable (mRS 0-2) and unfavorable (mRS 3-6) neurological outcome. In 22 patients, UCH-L1 levels were obtained for up to five days. In this subgroup, UCH-L1 measured at day five showed significant elevation from baseline levels in patients with unfavorable outcome (p=0.026). Elevated UCH-L1 levels at day five were higher in patients with unfavorable outcome than in patients with favorable outcome (p=0.001).
Elevated UCH-L1 levels during the five-day follow-up were associated with unfavorable neurological outcome. Repetitive measurements of UCH-L1 concentrations with an emphasis on change relative to the individual baseline could be the optimal approach for future clinical studies.
动脉瘤性蛛网膜下腔出血(aSAH)是导致长期残疾和死亡的常见原因。初次出血后,继发性脑损伤是死亡率和发病率的主要原因。尽管进行了广泛研究,但仍缺乏可靠的预后生物标志物。我们测量了aSAH患者的泛素羧基末端水解酶L1(UCH-L1)水平,以评估其预后潜力。这是首次将血浆UCH-L1作为aSAH患者潜在的预后生物标志物进行研究。
在这项基于人群的前瞻性研究中,对47例aSAH患者进行了长达五天的UCH-L1水平测量。在入住重症监护病房(ICU)后0、12和24小时以及此后每天测量UCH-L1,直至患者从ICU转出。仅纳入在aSAH后24小时内测量UCH-L1的患者。在aSAH后六个月,用改良Rankin量表(mRS)评估患者的神经功能结局。
在神经功能结局良好(mRS 0-2)和不良(mRS 3-6)的组之间,aSAH后最初24小时内的UCH-L1水平无显著差异。在22例患者中,获得了长达五天的UCH-L1水平。在该亚组中,第5天测量的UCH-L1在结局不良的患者中较基线水平显著升高(p=0.026)。结局不良的患者第5天升高的UCH-L1水平高于结局良好的患者(p=0.001)。
在五天随访期间UCH-L1水平升高与不良神经功能结局相关。重复测量UCH-L1浓度并强调相对于个体基线的变化可能是未来临床研究的最佳方法。