Context:

Stroke defines an acute vascular event in the brain and is a leading cause of death and disability. Ischemic stroke results from decreased blood flow to a portion of the brain with consequent cell death. Hemorrhagic stroke, on the other hand, is a result of bleeding into the brain. Ischemic stroke is far more common and is potentially treatable with thrombolytic therapy. While effective, the wide application of this therapy has been hampered by restrictive selection criteria based on time since onset of symptoms. Successful treatment requires a system capable of rapidly identifying and evaluating prospective candidates. In this context, use of community education, specific ED protocols and designated treatment centers may demonstrate some advantages. Evidence is emerging that patient selection by time since stroke onset, imaging characteristics, and intra-arterial treatment may increase the probability of recanalization of occluded vessels. Normalization of serum glucose, acute blood pressure management and surgical extraction of intracerebral clot may be of benefit in some circumstances.

Objectives:

The purpose of this report is to systematically review the available literature in the field of acute stroke evaluation and treatment. The University of Ottawa Evidence-based Practice Center (UO-EPC) task involving the following three areas: (1) what interventions in acute stroke (<24 hours from onset) are effective in reducing morbidity and mortality (2) how safety and effectiveness of these interventions vary by timing in relation to onset of symptoms and (3) determine what the evidence is that specific systems of care improve outcomes of acute stroke.

Data Sources:

The databases searched were MEDLINE^® (1966 to April Week 4 2004), Embase (last 6 months) and CINAHL (1982 to April Week 5 2004) using the OVID interface. Also searched were the Stroke Trials Directory, the Cochrane Stroke Group Registry, conference proceedings from the 28^th International Stroke Conference 2003 (Stroke, Feb 2004) and the American Academy of Neurology Annual Meeting (published in Neurology). The Effective Practices and Organization of Care (EPOC) registry was searched by the Cochrane review group.

Study Selection:

All results of searches for evidence were provided to two reviewers for assessment. All studies were screened by both reviewers by reviewing the bibliographic records, and when meeting inclusion criteria, the subsequent full-text of the record. If the reviewers did not agree in finding at least one unequivocal reason for excluding the study, it was entered into the next phase of the review. The reasons for exclusion were noted using a modified QUOROM format.

Data Extraction:

Two reviewers independently abstracted the contents of each included study using an electronic Data Abstraction form developed especially for this review. Data abstracted included the study and population characteristics, intervention characteristics and relevant outcomes of included studies.

Data Synthesis:

Attempts were made to minimize, and where not possible, explain statistical and clinical heterogeneity. Pooled estimates were only calculated if clinically and statistically appropriate. In situations where it was felt to that quantitative synthesis could not be performed, a qualitative narrative synthesis was conducted.

Results/ Conclusions:

Currently, available data do not support a role for surgery in the treatment of acute intracerebral hemorrhage. Results, however, do not preclude benefit from surgery which involves modalities other than those studied in the acute trials (e.g., minimally invasive technologies) or treatment of hemispheric hematoma at very early timeframes. Further, the available literature did not comment on cerebellar hematoma and thus this analysis does not apply to infratentorial hemorrhage.

In spite of potential importance, availability of therapy and ease of administration of antihypertensive agents, very little data exists to suggest that their use is of benefit (or results in harm) in the setting of acute ICH. A similar situation exists regarding glucose management for acute ischemic stroke. Further studies are required in both these areas.

IV thrombolysis with tPA is effective and efficacious for acute ischemic stroke within 3 hours of symptom onset. The effectiveness is strongly linked to time since onset of symptoms with shorter times demonstrating significantly better outcomes. Patient level meta-analysis suggests that treatment may be effective up to 270 minutes with treatment increasing the odds of death beyond 270 minutes. Further work is needed to define the risks and benefits of treatment outside the 3 hour window prior to advocating widespread use in these patients. Intra-arterial therapy remains an option for a subgroup of patients with large vessel occlusions principally in the middle cerebral artery distribution. The evidence for this intervention, however, remains less robust than for IV therapy. Limited data is available regarding patient characteristics predicting outcome. The system changes required to ensure prompt delivery of appropriate therapy are complex and operate on multiple levels. In spite of their critical role, little data exists regarding the efficacy of these interventions and, in particular, the relative efficacy of various components with regard to patient outcomes.

Ultrasound for enhancement of thrombolysis in the setting of MCA occlusion has suggested efficacy in 2 studies and a definitive trial to demonstrate the benefit and risks is required.

CT and MRI imaging for patient selection and prediction of outcome in thrombolysis has yet to be prospectively evaluated. The two included CT studies differ in onset to evaluation time with only a weak correlation between CT changes and outcome seen in the trial enrolling patients from 0–6 hours. Neither study quantified CT changes. The ASPECTS score is an easily quantifiable scoring system for early infarct changes. Retrospective evaluation of the ASPECTS score suggests that values below 7 correlate with poorer outcomes. As CT is widely available this system deserves further exploration. Additional information relevant to treatment decisions may be provided by CT angiography. Occlusion of proximal vessels is associated with higher rates of infarction and thus may influence treatment modalities.

MRI DWI lesions correlate with the presence of infarcts in small cohorts of patients and time to peak measures on early scans may correlate with recanalization after IV tPA treatment. These findings require reproduction and further evaluation. The multiplanar abilities and potential for acquisition of multiple parameters are potentially attractive features of this modality and may assist in selecting patients with a greater ratio of benefit to harm in intravenous and intra-arterial treatment paradigms.

The narrow time window for thrombolysis in acute stroke as well as the relationship between time to treatment and outcome has led to the exploration of a number of strategies for optimization of outcomes. Community education programs regarding the symptoms of stroke have not been independently evaluated but rather studied in the context of more comprehensive system changes. Thus it is unclear if these programs are effective in improving patient outcomes. Further exploration is also required regarding the content and targeting of such programs. Descriptions of designated treatment centers have shown the feasibility of this approach but an evaluation of published criteria for and marginal effectiveness of such designations remains to be performed.