| Background:The incidence of ischemic stroke showed a rising trend in China every year, with high disability, mortality and recurrence rate. It become the hot issues of governments of the world. Compared with the prevention of ischemic stroke, the treatment in acute phase of ischemic stroke is lagging behind. Currently acute ischemic stroke effective treatment is still focused on the antithrombotic, anticoagulant, thrombolytic and check-stroke unit. Recent randomized controlled trials(IMS-3,SYNTHESIS,MR RESCUE) fail to demonstrate any significant benefit of endovascular therapy than intravenous thrombolysis in acute ischemic stroke[1-3]. The latest trials of SWIFT PRIME, EXTEND IA and ESCAPE testify the advantage of endovascular treatment from 2014 to April 2015[4-6]. All studies confirm endovascular treatment can improve the prognosis of patients three months and improve the revascularization rates with a lower mortality significantly, without increasing the risk of cerebral hemorrhage. So the endovascular treatment become one of the highlights against the acute phase of ischemic stroke.Another highlight is the Aggressive medical management including(loading dose of statins and dual antiplatelet aggregation joint) for ischemic stroke, which is first proposed in SAMMPRIS study in 2011, showing that aggressive medical management can benefit more than endovascular treatment for the treatment of intracranial arterial stenosis[7]. It is reported that Aggressive medical management, especially statin use can significantly improve the survival rates of acute ischemic stroke, and even the traumatic brain injury, cerebral hemorrhage prognosis. Correlation studies have shown that antecedent use of statins prior to intracerebral hemorrhage(ICH) is associated with favorable outcome and reduced mortality after ICH[8]. However, the exact mechanism of the treatment with aggressive medical management in patients with acute ischemic stroke is unclear. Some people think it is because the coaction of antithrombotic, anti-inflammatory and antioxidant in aggressive medical management. One of speculated reasons is the reperfusion of infarct region improved by multiple mechanisms.Cerebral perfusion in neurology is a hot issue. Perfusion technology include CT perfusion imaging, PET-CT examination and MRI perfusion imaging technology the frist two of which have corresponding radiation hazards and need for injection of contrast agent resulting in a failure repeated testing. MRI perfusion imaging techniques is divided into two imaging techniques based on imaging contrast agents need, one is dynamic susceptibility contrast imaging technique(bolus dynamic susceptibility contrast, DSC), the other is the arterial spin labeling technique(Arterial Spin Labeling, ASL) without injection of contrast agent. DSC techniques have been the main MR perfusion imaging method used in acute ischemic stroke. In particular, time to the maximum of the tissue residual function(Tmax) has been applied in large case series and clinical trials to define regions of hypoperfusion. But it is an invasive examination of kidney function injury and poor reproducibility. Arterial spin-labeled(ASL) techniques provide cerebral blood flow(CBF) measures reflecting microvascular perfusion distribution and perfusion without the use of a contrast agent by magnetically tagging the water in inflowing blood. It is commonly used in perfusion imaging and angiography, with advantages of noninvasive, easy, repeatable, and good repeatability[9]. Recent studies have shown that ASL can replace the traditional MRI perfusion imaging technology which is need contrast agents to assess reperfusion, and identifies clinical outcome after acute ischemic stroke[10]. Armin Eilaghi et al showed that reperfusion was a stronger predictor of infarct volume and clinical outcome than recanalization[11-12]. Future prognostic models for clinical outcome in patients with acute ischemic stroke therefore should consider reperfusion. Currently, selecting appropriate imaging techniques to evaluate their efficacy have been fully used in patients with endovascular treatment, but the perfusion changes and prognosis of acute ischemic stroke with aggressive medical treatment have not been reported before. At the same time,the influence of early reperfusion and prognosis in acute ischemic stroke with aggressive medical treatment have not been reported. For the above reasons, this study used arterial spin labeling technique to discuss the reperfusion in patients with acute ischemic stroke with aggressive medical management after 24 hours compared with treatment before, and to follow up their clinical prognosis in those acute ischemic stroke patients who cannot carry on thrombolytic therapy and endovascular treatment, and to provide more clinical guidance.Objective:The aim of this study was to investigate cerebral reperfusion and outcome in patients treated with aggressive medical management for acute ischemic stroke by using the magnetic resonance imaging perfusion-arterial spin labeling imaging(ASL),and to explore the relationship between early reperfusion and clinical outcomes for acute ischemic stroke.Materials and Methods:1.The inclusion and exclusion criteriaThe inclusion criteria: the study enrolled consecutive patients within 72 hours and more than 6 hours of stroke onset based on the following inclusion criteria: the diagnosis of ischemic stroke was confirmed by diffusion-weighted imaging(DWI) showing evidence of acute unilateral cerebral hemisphere infarction(Anterior circulation infarction); age 18 years or older; 4≤NIHSS score ≤24; patient or patient’s next of kin capable of informed consent;The exclusion criteria: hemorrhage; other conditions, such as vascular malformation, tumor, abscess, or other major nonischemic brain disease; a clear indication for anticoagulation therapy(presumed cardiac source of embolus, such as atrial fibrillation or prosthetic cardiac valve); contraindication to clopidogrel, aspirin or statins; bilateral strokes or any acute endovascular or Intravenous Thrombolysis; gastrointestinal bleeding or major surgery within the previous 3 months. Patients receiving other drug for reperfusion therapy before a second MRI examination were excluded.2.MRI ProtocolPatients enrolled in the study had two ASL studies performed, the first before aggressive medical management and the second 24 hours later Patients were scanned with MRI before aggressive medical management and the second 24 hours later. Siemens Trio 3.0 T MR machine was used to get the imaging. First of all, conventional T1 WI, T2 WI sequence was applied to discharge other nervous system diseases without ischemic stroke, then we collected the imaging of magnetization prepared rapid acquisition gradient echo collection, finally, pulsed arterial spin labeling imaging was acquired. They all had good qualities for all imaging dates(routine MRI examination showed no motion artifacts and other interference).CBF maps were preprocessed by SPM 8 software and compared by two-sample t test between pre- and post-treatment.3.Follow-upDuration of treatment and follow-up was 3 months. Before and in 90 d after the treatment, the degree of neurological deficit was evaluated by National Institutes of Health Stroke Scale(NIHSS), daily living skills assessment were assessed by modified Rankin Score(mRS).The primary outcome was stroke(ischemic or hemorrhagic), myocardial infarction, hemorrhagic events and the recovery of neurological function during 90 days of follow-up in an intention-to treat analysis.Results:15 patients had confirmed acute stroke and completed follow-up. There were 8 males, 7 females; age 38-70 years old, average age(55 ±9.5) years old. Patients admission average NIHSS score were 7.20±2.76, At 7d,after treatment, the NIHSS score were 5.47±2.56,and the difference was significant(P < 0.01). Patients admission average mRS were 3.93±0.26,In 90 d after the treatment, the average mRS score were 3.00±0.66,and there was significant change in mRS(P < 0.05). During the 90 day follow-up, There was no occurrence of any stroke in all patients. The improvement of the regional cerebral blood flow(rCBF) was profoundly more than before which was displayed by the ASL 24 hours after treatment(P<0.05)and are mainly located in the left caudate, right anterior cingulate and right middle temporal gyrus. There is no brain area of the regional cerebral blood flow decreased significantly.Conclusion:1.Aggressive medical management can improve the early reperfusion for acute ischemic stroke effectively without steal phenomenon and also improve neurological function by improving cerebral blood flow with good security.2.The improvement of neurological function at discharge and 90-day good prognosis through aggressive medical management may be associated with greater early reperfusion of Infarct regions.3.Arterial spin labeling technique has good sensitivity and high specificity for assessing perfusion in patients with acute ischemic stroke.4. Further design of randomized controlled trial would provide more scientific evidence for the treatment of aggressive medical management on acute ischemic stroke. |
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