After basic stabilization of ABCs—airway maintenance, breathing and ventilation, and circulation— a brief but thorough neurologic examination is critical to define severity of neurologic injury and to help localize injury. Some standardized tools help with rapid assessment, including the NIHSS. The NIHSS is a standardized and reproducible evaluation that can be performed by many different specialties and levels of healthcare providers and provides information about stroke severity, localization, and prognosis.5 NIHSS offers free online certification.
Imaging: Early brain imaging and interpretation is another important piece of the acute evaluation of stroke. The most commonly used first-line imaging is noncontrast head CT, which is widely available and quickly performed. This type of imaging is sensitive for intracranial hemorrhage and can help distinguish nonvascular causes of symptoms such as tumor. CT is not sensitive for early signs of infarct, and, most often, initial CT findings are normal in early ischemic stroke. In patients who are candidates for intravenous fibrinolysis, ruling out hemorrhage is the main priority. Noncontrast head CT is the only imaging necessary to make decisions regarding IV thrombolytic treatment.
For further treatment decisions beyond IV tPA, intracranial and extracranial vascular imaging can help with decision making. All patients with stroke should have extracranial vascular imaging to help determine the etiology of stroke and evaluate the need for carotid endarterectomy or stenting for symptomatic stenosis in the days to weeks after stroke. More acutely, vascular imaging can be used to identify large vessel occlusions, in consideration of endovascular intervention (discussed in further detail below). CT angiography, magnetic resonance (MR) angiography, and conventional angiography are all options for evaluating the vasculature, though the first two are generally used as a noninvasive first step. Carotid ultrasound is often considered but only evaluates the extracranial anterior circulation; posterior circulation vessel abnormalities (like dissection) and intracranial abnormalities (like stenosis) may be missed. Although tPA decisions are not based upon these imaging modalities, secondary stroke prevention decisions may be altered by the findings.4
Perfusion imaging is the newest addition to acute stroke imaging, but its utility in guiding decision making remains unclear. Perfusion imaging provides hemodynamic information, ideally to identify areas of infarct versus ischemic penumbra, an area at risk of becoming ischemic. The use of perfusion imaging to identify good candidates for reperfusion (with IV tPA or with interventional techniques) is controversial.9 It is clear that perfusion imaging should not delay the time to treatment for IV tPA within the 4.5-hour window.
(click for larger image)Table 2. Inclusion and exclusion criteria for IV tPA treatmentInclusion and Exclusion Criteria of Patients Presenting within Three Hours of Symptom Onset for IV tPA Therapy4
Windows: Current guidelines for administration of IV tPA for acute stroke are based in large part on two pivotal studies—the NINDS tPA Stroke Trial and the European Cooperative Acute Stroke Study III (ECASS III).6,7 IV alteplase for the treatment of acute stroke was approved by the FDA in 1996 following publication of the NINDS tPA Stroke Trial. This placebo-controlled randomized trial of 624 patients within three hours of ischemic stroke onset found that treatment with IV alteplase improved the odds of minimal or no disability at three months by approximately 30%. The rate of symptomatic intracranial hemorrhage was higher in the tPA group (6.4%) compared to the placebo group (0.6%), but mortality was not significantly different at three months. Though the benefit of IV tPA was clear in the three-hour window, subgroup analyses and further studies have clarified that treatment earlier in the window provides further benefit.
Given the difficulty of achieving treatment in short time windows, further studies have aimed to evaluate the utility of IV thrombolysis beyond the three-hour time window. While early studies found no clear benefit in extending the window, pooled analyses suggested a benefit in the three to 4.5-hour window, and ECASS III was designed to evaluate this window. This randomized placebo-controlled study used similar inclusion criteria to the NINDS study, with the exception of the time window, and excluded patients more than 80 years old, with large stroke (NIHSS score greater than 25), on anticoagulation (regardless of INR [international normalized ratio]), and with a history of prior stroke and diabetes. Again, in line with prior findings of time-dependent response to tPA, the study found that the IV tPA group were more likely than the placebo group to have good functional outcomes at three months, but the magnitude of this effect was lower than the one seen in the studies of the zero- to three-hour window. The rate of symptomatic intracranial hemorrhage in the 4.5-hour window was 7.9% using the NINDS tPA Stroke Trial criteria.