Charlotte Zerna, MD, MSc
@CharlotteZerna
Mechanical thrombectomy for acute ischemic stroke in the anterior circulation due to large-vessel occlusion (LVO) has been established as the new standard of care. The ESCAPE trial found no evidence of treatment heterogeneity between subjects in the early and late windows, and treatment effect favoring intervention was seen across all clinical outcomes in the extended time window.1 The DAWN and DEFUSE 3 trials were then further able to show benefit of mechanical thrombectomy > 6 hours from onset for patients selected by clinical-core mismatch or perfusion-core mismatch via advanced neuroimaging.2, 3 But even though benefit clearly exists beyond 6 hours, fast mechanical thrombectomy is critical since an LVO acute ischemic stroke typically leads to destruction of 1.9 million neurons, 14 billion synapses, and 12 km (7.5 miles) of myelinated fibers per minute.4 Because LVO can only be diagnosed by time-efficient neurovascular imaging, the authors implemented a CTA-for-All stroke imaging policy in their regional health system for all patients presenting within 24 hours of last known well, regardless of baseline NIHSS scores and eliminating the requirement of obtaining baseline creatinine levels. The new policy applied to stroke codes in both the ED and on hospital floors, whereas before, an emergency CTA was reserved only for patients with acute ischemic stroke confirmed by non-contrast CT who presented within 6 hours of last known well and with an NIHSS score of at least 6 once serum creatinine levels were known.
In general, implementation led to more patients undergoing CTA, fast median time from ED arrival to CTA and higher detection rate of LVO (166 versus 96 patients; 32% versus 25% of all acute ischemic stroke, P=0.014). For early presenters (< 6 hours from last known well), mechanical thrombectomy was performed significantly faster after protocol implementation and thus more patients were discharged with a favorable outcome. This might have also been a result of lower NIHSS scores that were treated within this group. For late presenters (≥ 6 hours from last known well), the percentage of LVO patients who underwent mechanical thrombectomy doubled after protocol implementation, but no outcome difference at discharge was observed in such patients before and after protocol implementation. However, the authors scored patients on the Glasgow Outcome Scale at discharge instead of the more commonly used modified Rankin Scale at discharge or even at 3 months. Also, Alberta Stroke Program Early CT Scores were not available, and thus the analysis was not adjusted for early ischemic changes, a known important predictor of outcome.
Regardless of the limitations of this study, performing emergent neurovascular imaging for acute ischemic strokes should be standard of care. LVO detection in moderate to severe strokes is crucial to offer guideline-based treatment (i.e., mechanical thrombectomy). The CTA-For-All policy improved LVO detection, increased the mechanical thrombectomy rate, hastened intervention, and was thus associated with a trend toward improved outcome. Additionally, emergent neurovascular imaging gives crucial information for the minor stroke population as well. Multiple studies have shown the association of ≥ 50% stenosis or occlusion of the intracranial arteries with early neurological deterioration and poor outcome even when patients initially presented with mild symptoms.5 The detection of an intracranial stenosis or occlusion is not just about offering mechanical thrombectomy but also considering intravenous alteplase and other supportive therapies such as blood pressure management. Furthermore, non-randomized evidence from a systematic review and meta-analysis performed in 2017 suggests that CTA/CT perfusion are not associated with a statistically significant increase in risk of acute kidney injury in patients with stroke, even those with known chronic kidney disease.6 Acute ischemic stroke is a medical emergency, and it is time that the utilization of our available diagnostic tests reflects that.
References:
1. Evans JW, Graham BR, Pordeli P, Al-Ajlan FS, Willinsky R, Montanera WJ, et al. Time for a Time Window Extension: Insights from Late Presenters in the ESCAPE Trial. AJNR American journal of neuroradiology. 2017.
2. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. The New England journal of medicine. 2018;378:11-21.
3. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. The New England journal of medicine. 2018.
4. Saver JL. Time is brain–quantified. Stroke; a journal of cerebral circulation. 2006;37:263-6.
5. Coutts SB, Modi J, Patel SK, Aram H, Demchuk AM, Goyal M, et al. What causes disability after transient ischemic attack and minor stroke?: Results from the CT and MRI in the Triage of TIA and minor Cerebrovascular Events to Identify High Risk Patients (CATCH) Study. Stroke; a journal of cerebral circulation. 2012;43:3018-22.
6. Brinjikji W, Demchuk AM, Murad MH, Rabinstein AA, McDonald RJ, McDonald JS, et al. Neurons Over Nephrons: Systematic Review and Meta-Analysis of Contrast-Induced Nephropathy in Patients With Acute Stroke. Stroke; a journal of cerebral circulation. 2017;48:1862-1868.
I would like to thank you Charlotte for this nice review of our “CTA-for-All” article. I could not agree more that immediate CTA with NCCT should be the standard of care for all stroke imaging performed with 24 hours of last known well.
My personal motivation for implementing this protocol and writing the paper was years of frustration watching missed opportunities as a neurointensivist, admitting patients to the ICU with massive, devastating strokes who initially presented to the ED well within the time widow for intervention. Informed of a “normal” NCCT, emergency medicine physicians may not always recognize a basilar artery occlusion, or might assign a clear hemispheric focal deficit to a seizure, metabolic syndrome, or even a psychogenic process. Or the neurological consultation is left for the next morning because the negative NCCT “ruled out stroke.” Even more often, the deficit with an acute LVO may not seem so bad initially, but my experience is that the clinical exam usually catches up with the angiogram, albeit many hours later after millions of brain cells have died.
More stroke victims will have the opportunity to benefit from timely thrombectomy with widespread implementation of CTA-for-All. The time has come.