Pihlasviita Saana, Mattila Olli S, Nukarinen Tiina, Kuisma Markku, Harve-Rytsälä Heini, Ritvonen Juhani, Sibolt Gerli, Curtze Sami, Strbian Daniel, Pystynen Mikko, Tatlisumak Turgut, Lindsberg Perttu J
Neurology and Clinical Neurosciences, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Emergency Medicine and Services, Department of Emergency Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Front Neurol. 2024 Nov 7;15:1472424. doi: 10.3389/fneur.2024.1472424. eCollection 2024.
After severe ischemic stroke (IS), circulating levels of symmetric dimethylarginine (SDMA) increase. We investigated the early dynamics of SDMA in stroke to potentially aid with prehospital identification of severe IS from hemorrhagic stroke (HS).
We performed targeted mass spectrometry (MS) measurements of SDMA in two sequential acute plasma samples (early and secondary) of 50 IS patients with LVO and 49 HS patients. Secondary samples of 227 IS and 84 HS patients with moderate to severe symptoms (NIHSS ≥ 7) subsequently underwent ELISA validation.
The median (IQR) last-known-well (LKW) to sampling times were 43 min (35-67) for early samples in the MS analysis, and 83 min (65-113) for secondary samples in MS and ELISA analyses. No inter-group differences existed in early samples, but IS patients had significantly higher mean (IQR) SDMA levels in secondary samples in both analyses: 5.8 (5.3-6.9) vs. 5.1 (4.2-5.8) A.U. for HS, < 0.001, with MS; and 0.82 (0.72-1.01) vs. 0.71 (0.58-0.85) nmol/mL for HS, < 0.001, with ELISA. For IS patients, higher SDMA levels were associated with cardioembolic stroke: 0.84 (0.73-1.09) vs. 0.79 (0.71-0.91) nmol/mL for other etiologies, = 0.042, and poor outcome: modified Rankin Scale (mRS) 4-6; 0.90 (0.73-1.06) vs. 0.80 (0.72-0.97) nmol/mL for mRS 0-3 ( = 0.045).
In a large clinical cohort of stroke patients with moderate to severe symptoms, our data suggest that SDMA can assist in differentiation of IS and HS patients already 1 h and a half after symptom onset. SDMA may prove to have future value in a diagnostic stroke biomarker panel.
严重缺血性卒中(IS)后,对称二甲基精氨酸(SDMA)的循环水平会升高。我们研究了卒中患者SDMA的早期动态变化,以潜在地帮助在院前鉴别严重IS与出血性卒中(HS)。
我们对50例伴有大血管闭塞的IS患者和49例HS患者的两份连续急性血浆样本(早期样本和二次样本)进行了SDMA的靶向质谱(MS)测量。随后,对227例中度至重度症状(美国国立卫生研究院卒中量表[NIHSS]≥7)的IS患者和84例HS患者的二次样本进行了酶联免疫吸附测定(ELISA)验证。
在MS分析中,早期样本从最后已知正常状态(LKW)到采样时间的中位数(四分位间距)为43分钟(35 - 67分钟),在MS和ELISA分析中,二次样本的该时间为83分钟(65 - 113分钟)。早期样本组间无差异,但在两项分析中,IS患者二次样本中的SDMA平均水平(四分位间距)显著更高:对于HS患者,MS分析中分别为5.8(5.3 - 6.9)与5.1(4.2 - 5.8)任意单位,P < 0.001;ELISA分析中分别为0.82(0.72 - 1.01)与0.71(0.58 - 0.85)nmol/mL,P < 0.001。对于IS患者,较高的SDMA水平与心源性栓塞性卒中相关:其他病因组为0.84(0.73 - 1.09)与0.79(0.71 - 0.91)nmol/mL,P = 0.042;与不良预后相关:改良Rankin量表(mRS)4 - 6分者为0.90(0.73 - 1.06)与mRS 0 - 3分者的0.80(0.72 - 0.97)nmol/mL,P = 0.045。
在一个具有中度至重度症状的卒中患者大型临床队列中,我们的数据表明,SDMA在症状发作后1个半小时即可帮助鉴别IS和HS患者。SDMA可能在诊断性卒中生物标志物组合中具有未来价值。