| Reworded | An AIS assessment team, consisting of physicians and nurses, should be established to conduct meticulous and standardised neurological examinations. | I | B |
| Trained stroke emergency providers can rapidly and accurately identify a stroke and safely treat patients who had a stroke with intravenous rt-PA or TNK, and/or IA MT.7
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| Reworded | The NIHSS score is recommended to assess stroke severity. | I | B |
| New recommendation | Dedicated image systems should be established to provide early neuroimaging examinations for patients who may qualify for intravenous thrombolysis and/or IA MT. | I | B |
| The earlier patients complete the neuroimaging examinations, the sooner they can receive intravenous thrombolysis or IA MT, thus increasing the likelihood of re-establishing the perfusion.8–12
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| New recommendation | Emergency brain image assessment should be conducted in all patients on the first arrival with suspected acute stroke before receiving any specific therapy. | I | A |
| Brain imaging helps physicians diagnose intracranial haemorrhage (ICH), assess for infarction size, location, vascular distribution, severity, and find an LVO, and make immediate and long-term treatment decisions.13–16 For some patients with stroke upon wake-up, or unknown onset time, or within 4.5–9 hours, multimode brain imaging helps identify patients with AIS who may benefit from intravenous thrombolysis or IA MT and guide further treatment plans.17–19
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| Reworded | Patients with suspected AIS should preferably undergo brain imaging within 30 min upon arrival at the emergency department. | I | B |
| New recommendation | A non-contrast CT (NCCT) scan is the first to be done to rule out an ICH. Then, initiate thrombolytic therapy as soon as possible. | I | B |
| Although MRI and NCCT have equal efficiency in excluding ICH, NCCT is faster to identify an ICH (MRI: 13 min (10–16); NCCT: 9 min (7–12); p<0.001).20–23 Patients who had MRI and were treated with intravenous rt-PA or IA MT had a significant intrahospital delay of about 20 min.24 As the benefit of intravenous thrombolysis is time independent, NCCT should be completed as quickly as possible. Treatment should not be delayed by considering multimodal MRI or CT imaging. |
| Reworded | In patients qualified for thrombolysis, initiating thrombolytic therapy should not be delayed by considering multimodal CT or magnetic resonance perfusion (MRP) studies. | I | B |
| New recommendation | For patients with wake-up stroke, stroke with an unknown onset time, or stroke occurring within 6–24 hours, CT angiography (CTA)+CT perfusion (CTP) or magnetic resonance angiography (MRA)+MRI is recommended to assess the potential benefits of intravenous thrombolysis or IA MT. | IIa | A |
| In the DAWN trial, the NIHSS scores and core infarction mismatch on CTP or diffusion-weighted imaging (DWI) are used as eligible criteria for selecting patients with anterior circulation LVO within 6–24 hours for IA MT. The 90-day functional outcome in the MT group was significantly superior to that in the control group (modified Rankin Scale (mRS) 0–2, 49% vs 13%, adjusted difference 0.33, 95% CI 21 to 44).18 The DEFUSE 3 trial used CTP or DWI–perfusion-weighted imaging (PWI) perfusion-core mismatch and maximum core size to select patients with anterior circulation LVO within 6–16 hours for IA MT. It terminated early since patients treated with IA MT did better than those who received standard medical therapy (mRS 0–2, 44.6% vs 16.7%, rate ratio (RR)=2.67, 95% CI 1.60 to 4.48, p<0.001).25 The MR WITNESS trial used a quantitative mismatch of DWI-MRI with fluid-attenuated inversion recovery (FLAIR) to select patients for intravenous rt-PA with an onset >4.5 hours. About 39% of patients achieved mRS 0–1 at 90 days. One patient had an sICH (1.3%), and three developed symptomatic oedema (3.8%).19
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| Reworded | Patients with suspected LVO and without a history of renal impairment can have the head and neck CTA first before obtaining serum creatinine to avoid delay in treatment. | I | B |
| New recommendation | For patients with AIS upon wake-up or unknown time of onset >4.5 hours, if MRI showed a DWI-positive/FLAIR-negative region of infarct, intravenous thrombolysis can be considered. | IIa | B |
| The WAKE-UP trial selected patients who had a stroke with an unclear onset time >4.5 hours and an ischaemic lesion visible on DWI but no parenchymal hyperintensity on FLAIR for intravenous rt-PA. These patients had a significantly better functional outcome (53.3% vs 41.8%, adjusted OR 1.61, 95% CI 1.09 to 2.36, p=0.02) but also more sICH (2.0% vs 0.4%, adjusted OR 4.95, 95% CI 0.57 to 42.87, p=0.15) than placebo at 90 days.17 For patients with AIS upon wake-up, or within 4.5–9 hours, the benefits of intravenous rt-PA in patients with AIS with an imaging mismatch were associated with better outcomes and showed no significant differences in the risk of ICH.9
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| New recommendation | For patients with suspected LVO, MRA or CTA should be completed as soon as possible to determine the eligibility for IA MT. | I | A |
| Identification of an LVO requires either a CTA or MRA. Two comparative studies evaluated the sensitivity of CTA, MRA and digital subtraction angiography (DSA) to diagnose intracranial stenosis and occlusion.26 27 CTA had a significantly higher positive predictive value for stenosis (93% vs 65%, p<0.001) and occlusion (100% vs 59%, p<0.001) than MRA.26 27 The sensitivity of CTA and MRA for the diagnosis of LVO ranges from 87% to 100% compared with the gold-standard DSA.27 As the efficacy of IA MT is time-dependent, the vascular image should be conducted as quickly as possible.28
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| New recommendation | For patients with indications for IA MT, performing a vascular imaging of extracranial carotid and vertebral arteries helps the approach for IA MT. | IIb | C |
| Most studies focused on the effectiveness of IA MT for AIS excluded patients with tandem occlusions. A retrospective review showed that treating tandem extracranial carotid artery steno-occlusion with IA MT, 42% had better outcomes and 88% had successful reperfusion.29
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| New recommendation | For patients with indications for IA MT, the assessment of collateral flow may help select treatment. | IIb | C |
| The MR CLEAN-LATE trial enrolled patients with collateral flow in the middle cerebral artery (MCA) territory of the affected hemisphere on CTA within 6–24 hours of onset and found IA MT was effective and safe.30 In the DAWN trial, better collaterals, defined with the Tan scale by CTA or the American Society of Interventional and Therapeutic Neuroradiology grade by DSA, were associated with slower stroke progression and better functional outcomes.31 Hypoperfusion intensity ratio (HIR), defined as Tmax >10 s volume/Tmax >6 s volume, was independently associated with the collateral status. Poor collateral status (high HIR) was related to rapid infarct growth in the DEFUSE trial.32
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| Reworded | For patients with AIS with LVO in the anterior circulation presenting 6–24 hours after onset, it is recommended that CTP or DWI with PWI be completed. Patients selected for IA MT should follow the same eligibility criteria of the two major RCTs (DAWN and DEFUSE 3). | IIa | B |
| New recommendation | For patients with AIS with suspected BAO presenting between 6 and 24 hours of onset, CTA, MRA or DSA should be completed. Patients selected for BAO MT should follow the same eligibility criteria of the ATTENTION or BAOCHE. | IIa | B |
| The ATTENTION trial used CTA/MRA/DSA to select patients with BAO within 6–12 hours of onset and a baseline NIHSS ≥10 for IA MT. About 46% of the patients treated with IA MT had better outcomes compared with 23% treated with the best medical care (adjusted RR, 2.06; 95% CI 1.46 to 2.91; p<0.001).4 The BAOCHE trial also used CTA/MRA/DSA to select patients with BAO within 6–24 hours of onset and a baseline NIHSS ≥10 for MT. About 46% treated with IA MT had better outcomes compared with 24% treated with the medical care (adjusted RR, 1.81; 95% CI 1.26 to 2.60; p<0.001). Both trials observed a higher rate of sICH in the IA MT group.5
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| New recommendation | MRI is not routinely recommended to exclude cerebral microbleeds (CMBs) in patients eligible for intravenous thrombolysis. | I | A |
| Although the presence of CMBs and high CMB burdens is related to sICH in patients treated with intravenous rt-PA, one meta-analysis indicated the prevalence of CMBs on pretreatment MRI was not associated with a higher risk of early sICH (OR 1.74, 95% CI 0.91 to 3.33, I2=44.5%).33–36 Besides, both NINDS and ECASS III Studies did not exclude these patients.37 38
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| Unchanged | Less than 10 CMBs on MRI may be safe for intravenous thrombolysis. | IIa | B |
| Reworded | There is an increased risk of sICH in patients with >10 CMBs on pre-thrombolysis MRI. The clinical benefit of thrombolysis is unclear. If there may be significant potential benefits, intravenous thrombolysis may be reasonable. | IIb | B |
| Reworded | All patients should undergo blood glucose testing before intravenous thrombolysis. | I | B |
| Reworded | A baseline 12-lead ECG is recommended but should not delay the initiation of intravenous thrombolysis. | I | B |
| Reworded | Laboratory tests, including electrolytes, renal function, complete blood count with platelet count, coagulation function with international normalised ratio (INR) and cardiac ischaemia biomarkers, are recommended but should not delay the initiation of intravenous thrombolysis or IA MT. | I | C |
| Unchanged | Considering the low incidence of platelet abnormalities and coagulation dysfunction in the general population, intravenous thrombolysis should not be delayed while waiting for the results of platelet counts. | IIa | B |
| Revised | The benefits of chest X-rays in patients with hyperacute stroke are uncertain in the absence of evidence of acute pulmonary, cardiac or pulmonary vascular disease. If needed, it should not delay the initiation of intravenous thrombolysis. | IIb | B |
| Chest radiographs could provide information on pulmonary disease, cardiac disease, cardioembolic stroke and even aortic dissection based on the mediastinal width-to-chest ratio on chest X-ray.39 40 However, patients with a chest X-ray had significantly higher door-to-needle time than those had it after the treatment (75.8 vs 58.3 min, p=0.0001). |
| Reworded | The Alberta Stroke Program Early CT Score (ASPECTS) is recommended to provide guidance for IA MT. However, the decision-making doctor must have the training in calculating ASPECTS. | IIa | B |
| New recommendation | When assessing the benefits of IA MT for patients with AIS within 6 hours who have LVO in the anterior circulation and an ASPECTS ≥6, CT+CTA or MRI+MRA is preferably recommended. | I | A |
| IA MT for patients with an ASPECTS ≥6 and an anterior circulation LVO is more effective than those with an ASPECTS <6.41 In the MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT and THRACE trials, only THRACE and MR CLEAN trials used NCCT to select patients for IA MT, while the other four RCTs used CT+CTA or MRI+MRA.42–47
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