Acute Ischaemic STROKE: From LABoratory to(2) the Patient's BED. Retrospective Study of Blood Biomarkers and Neuroimaging as Predictors of Cerebral Edema, Extension of Ischemic Injury and Functional Outcome
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 200
- 主要终点
- The occurrence of relevant Haemorrhagic Transformation
研究概览
简要总结
Background: Recanalization strategies have radically changed the outcome in a significant part of stroke patients. The unpredictable occurrence of cerebral edema (CE) and hemorrhagic transformation (HT) are frequent events in patients affected by ischemic stroke, even when an effective vessel recanalization has been achieved. These complications, related with blood brain barrier (BBB) disruption, remain difficult to prevent or treat, and antagonize the beneficial effect of successful recanalization, leading to poor outcome.
Aim: to shed light on the reperfusion injury biological bases, this study aims at evaluating the effects of circulating and imaging biomarkers in relation to CE and HT both in stroke patients and in a coherent murine stroke model. A close interaction between clinical and preclinical research could lead to a broader understanding of the results deriving from the individual lines of activity, allowing a deeper interpretation of the underlying phenomena.
Methods: The clinical setting is a retrospective observational study enrolling consecutive patients with acute ischemic stroke in the anterior circulation territory, treated with reperfusion therapies, at Careggi University Hospital in Florence (Italy) from October 1, 2015 to May 31, 2020. In this cohort, the investigators will apply a new approach to assess the presence of CE and HT after stroke in CT scans, through the quantification of anatomical distortion (AD) (induced by fluid extravasation in brain tissue) at 24 hours. A large panel of blood biomarkers related to inflammation, endothelial dysfunction , and fibrin resistance to lysis, will be measured as blood samples are taken from each patient before and 24 hours after thrombolysis or thrombectomy. The role of both AD and blood biomarkers as predictors of 3 months functional outcome, assessed by modified Rankin Scale (mRS), will be estimated.
Using a translational approach the investigators will develop a new mouse model of light-induced occlusion/reperfusion of the middle cerebral artery (MCA) to better reproduce the human setting. Then, the investigators will assess functional impairment induced by stroke with and without recanalization at different time points and the investigators will assess through ex vivo experiments the insurgence of BBB alterations 24 hours after the lesion. Finally, the investigators will characterize the stroke volume and the inflammation one week after stroke.
详细描述
The purpose of the project is to evaluate the correlation of circulating biomarkers related to blood brain barrier disruption with the development of cerebral edema, hemorrhagic transformation and the extension of the ischemic area investigated with modern neuroimaging techniques, in order to identify predictors of reperfusion injury in patients undergoing revascularization therapies.
In parallel with the clinical study, the investigators will investigate mechanistic aspects on the correlation between neuronal degeneration and the alteration of vascular permeability. To this end, the investigators will use a combination of advanced microscopy techniques and vital fluorescent markings in a novel mouse model of ischemic stroke.
- Clinical setting: This is a monocentric retrospective observational study of patients with acute ischemic stroke who have undergone revascularization therapies (systemic thrombolysis, endovascular treatment) at the Stroke Unit of the Careggi University Hospital from 1 October 2015 to 31 May 2020. Patients' data will be entered in a dedicated register: demographics and clinical data as well as haematochemical and neuroimaging parameters covered by this study. Available circulating biomarkers and neuroimaging collected at hospital arrival and repeated 24 hours after interventions will be included in the analysis, as well as the clinical/functional outcome assessed 3 months after stroke according to the modified Rankin scale by visit or phone interview.
Laboratory protocol:
In our university hospital, in acute ischemic stroke patients blood samples are routinely collected before and 24 hours after reperfusion treatment (either intravenous thrombolysis or endovascular thrombectomy). The investigators could retrieve blood samples already used for a previous study (Piccardi et al. 2018) and still correctly stored and available in our biological bank: blood is collected in tubes both with anticoagulant and without anticoagulant. Tubes are then centrifuged at room temperature at 1500 x g for 15 minutes, and the supernatant is stored in aliquots at -80° C.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patients who deny their consent to data processing;
- •Baseline and follow-up clinical and radiological data consistent with stroke in the posterior circulation;
- •Pregnancy;
- •Age <18 years;
结局指标
主要结局
The occurrence of relevant Haemorrhagic Transformation
时间窗: Non-enhanced CT brain scans acquired at 24 hours after ictal event
The presence and grading of Haemorrhagic Transformation defined as haemorrhagic infarction type two or any type of parenchymal haemorrhage (PH1 and PH2) according to ECASS II classification (Larrue et al, 2001) on 24h Non-enhanced CT brain scan. \[PH1: Parenchymal hematoma type 1; PH2: Parenchymal hematoma type 2.\]
The occurrence of Haemorrhagic Transformation
时间窗: Non-enhanced CT brain scans acquired at 24 hours after ictal event
Defined according to the ECASS (European Cooperative Acute Stroke Study) II radiographic classification of hemorrhagic transformation after ischemic stroke (Larrue et al. 2001) on 24h Non-enhanced CT brain scan. \[HI1: Hemorrhagic infarction type 1; HI2: Hemorrhagic infarction type 2; PH1: Parenchymal hematoma type 1; PH2: Parenchymal hematoma type 2.\]
3 month clinical-functional outcome
时间窗: For each patient enrolled in the study the functional outcome is assessed 3 months after the ictal event
All stroke patients are followed-up 3 months after the ictal event in the out-patient clinic of Careggi University Hospital, and their functional outcome is assessed according to the modified Rankin Scale. The Modified Rankin Scale is a 6 point disability scale with possible scores ranging from 0 (no symptoms) to 5 (severe disability). A separate category of 6 is used for patients who expire.
The occurrence of Cerebral Edema
时间窗: Non-enhanced CT brain scans acquired at 24 hours after the ictal event
Defined according to Cerebral Edema Classification used by the Helsinki Stroke Thrombolysis Registry Group (Strbian et al. 2013) on 24h Non-enhanced CT brain scan. \[CED1= Focal brain swelling up to one-third of the hemisphere; CED2= Focal brain swelling greater than one-third of the hemisphere; CED3= Brain swelling with midline shift\]
次要结局
- Anatomical Distortion (AD) volume (ml)(Non-enhanced CT brain scans acquired at 2 timepoints: 1) Baseline = before rtPA administration or thrombectomy, 2) Follow-up at 24 hours)
- Corrected infarct volume (ml)(Non-enhanced CT brain scans acquired at 2 time points: 1) Baseline = before rtPA administration or thrombectomy, 2) Follow-up at 24 hours)
- Relative Anatomical Distortion (AD) volume (ml)(Non-enhanced CT brain scans acquired at 2 time points: 1) Baseline = before rtPA administration or thrombectomy, 2) Follow-up at 24 hours)