Guideline sources The following summarized guidelines for the evaluation and management of acute ischemic stroke (AIS) are prepared by our editorial team based on guidelines from the European Stroke Organisation (ESO 2023; 2022; 2017; 2016; 2015), the American Diabetes Association (ADA 2023), the U.S. Preventive Services Task Force (USPSTF 2022), the American Heart Association (AHA/ASA 2021; 2019; 2018; 2014), the European Stroke Organisation (ESO/ESSD 2021), the United States Department of Defense (DoD/VA 2019), the European Thyroid Association (ETA 2018), the American College of Emergency Physicians (ACEP 2015), and the American Heart Association (AHA 2011). 1 2 3 4 5 6 7 8 9 10 12 14 15 16 17 18 19 20 21 21 22 23 Definition https://web.pathway.md/diseases/recwd1RIpW03JSM4H 1/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway AIS is a rapid onset of cerebral function disturbance lasting more than 24 hours or leading to death that is caused by occlusion of blood vessels limiting blood supply to the brain. 21 Epidemiology AIS is caused due to cardioembolism (AF, VHD), arteroembolism (atherosclerotic disease in the extracranial cervical carotid or vertebral artery), lacunar (microatheroma with plaque rupture and microembolism), and embolic stroke of undetermined source (ESUS). Less common causes include arterial dissection, vasculitis, vasospasm, and hypercoagulable states. 22 Disease course The blockage of blood vessels limiting blood supply to a part of brain results in AIS, which causes clinical manifestations of sudden facial droop, arm weakness, slurred speech, dizziness, and visual disturbance. Disease progression may lead to cerebral infarction, paralysis, coma and death. 21 Prognosis and risk of recurrence All-cause mortality associated with AIS is 3-fold compared with the age-matched cohort. 23 Calculator Calculator Calculator ABCD score for stroke Alberta stroke program early CT ATRIA stro Guidelines 1. Screening and diagnosis Screening for intracranial atherosclerotic disease: insufficient evidence to recommend routine screening for asymptomatic intracranial atherosclerotic disease in adult stroke-free individuals. I 2. Classification and risk stratification Severity assessment: assess patients with AIS using a stroke severity rating scale, preferably the NIHSS. B 3. Diagnostic investigations General principles: obtain diagnostic evaluation for gaining insights into the etiology and planning optimal strategies for preventing recurrent stroke, completed or underway within 48 hours of the onset of stroke symptoms, in patients with ischemic stroke or TIA. B https://web.pathway.md/diseases/recwd1RIpW03JSM4H 2/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Brain CT/MRI, for acute evaluation: As per ASA/AHA 2021 guidelines, obtain brain CT or MRI to confirm the diagnosis of symptomatic ischemic cerebral vascular disease in patients with suspected stroke or TIA. B Show 3 more As per ASA/AHA 2019 guidelines, obtain emergency brain imaging on arrival to a hospital before initiating any specific treatment for AIS in all patients with suspected acute stroke. A Show 2 more Brain CT/MRI (for secondary prevention): insufficient evidence to recommend obtaining routine brain MRI to guide treatment selection for the prevention of recurrent stroke. I Show 2 more CT/MR angiography, for acute evaluation: As per ASA/AHA 2021 guidelines: Obtain CT angiography or MRA (or carotid ultrasound) to screen for carotid stenosis in patients with symptomatic anterior circulation cerebral infarction or TIA eligible for revascularization. B Consider obtaining MRA or CT angiography of the intracranial large arteries and extracranial vertebrobasilar arterial system to identify atherosclerotic disease, dissection, Moyamoya disease, or other etiologically relevant vasculopathies in patients with ischemic stroke or TIA. C As per ASA/AHA 2019 guidelines, obtain noninvasive vessel imaging of the intracranial arteries in the initial imaging evaluation of patients otherwise meeting criteria for mechanical thrombectomy. A Show 6 more CT/MR angiography (for secondary prevention): consider obtaining intracranial vessel imaging in some patients with AIS to provide additional information to guide the selection of appropriate secondary stroke prevention treatments. C Show 2 more Carotid and vertebral artery imaging: As per AHA 2021 guidelines, obtain noninvasive cervical carotid imaging with carotid ultrasound, CT angiography, or MRA to screen for carotid stenosis in patients with symptomatic anterior circulation cerebral infarction or TIA eligible for revascularization. B As per AHA 2019 guidelines: Consider obtaining imaging of the extracranial carotid and vertebral arteries in addition to the intracranial circulation to provide useful information on patient eligibility and endovascular procedural planning in patients being potential candidates for mechanical thrombectomy. C Obtain noninvasive imaging of the cervical carotid arteries routinely within 24 hours of admission in patients with nondisabling (mRS score 0-2) AIS in the carotid territory eligible for carotid endarterectomy or stenting. B Cardiac imaging: https://web.pathway.md/diseases/recwd1RIpW03JSM4H 3/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway As per AHA 2021 guidelines, consider obtaining echocardiography with or without contrast to evaluate for possible cardiac sources of or transcardiac pathways for cerebral embolism in patients with cryptogenic stroke. C Show 2 more As per AHA 2019 guidelines, consider obtaining echocardiography in some patients with AIS to provide additional information to guide the selection of appropriate secondary stroke prevention. C Show 2 more Laboratory tests: As per AHA 2021 guidelines: Consider obtaining blood tests including the following in patients with a confirmed diagnosis of symptomatic ischemic cerebrovascular disease to gain insight into risk factors for stroke and to inform therapeutic goals: CBC PT, PTT blood glucose hgb A1c creatinine fasting or nonfasting lipid profile. B Consider obtaining tests for the following as clinically indicated to identify contributors to or relevant risk factors for stroke in patients with cryptogenic stroke: markers of systemic inflammation inherited or acquired hypercoagulable state inherited diseases associated with stroke bloodstream or cerebral spinal fluid infections infections causing CNS vasculitis (such as human immunodeficiency virus and syphilis) drug use (such as cocaine and amphetamines). C As per AHA 2019 guidelines: Assess blood glucose levels before administering IV alteplase since hypoglycemia and hyperglycemia may mimic acute stroke presentations. B Obtain baseline troponin assessment in patients presenting with AIS without delaying initiation of IV alteplase or mechanical thrombectomy. B Electrocardiogram: As per AHA 2021 guidelines, obtain an ECG to screen for AF and atrial flutter and to assess for other concomitant cardiac conditions in patients with suspected stroke or TIA. B As per AHA 2019 guidelines, obtain baseline ECG in patients presenting with AIS without delaying initiation of IV alteplase. B Cardiac monitoring: obtain cardiac monitoring to screen for AF and other potentially serious cardiac arrhythmias requiring emergency cardiac interventions. Obtain cardiac monitoring for at https://web.pathway.md/diseases/recwd1RIpW03JSM4H 4/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway least the first 24 hours. B Show 2 more Chest radiography: insufficient evidence to support the use of CXRs in the hyperacute stroke setting in the absence of evidence of acute pulmonary, cardiac, or pulmonary vascular disease. Avoid unnecessarily delaying the administration of IV alteplase to obtain CXRs. I Screening for thrombophilic states: insufficient evidence to recommend screening for thrombophilic states in patients with ischemic stroke. I Show 2 more Screening for dyslipidemia: consider assessing the plasma lipid profile (fasting or nonfasting) for estimating atherosclerotic CVD risk and documenting baseline LDL-C in 20 years old adult patients not on lipid-lowering therapy. B Screening for diabetes mellitus: As per AHA 2021 guidelines, consider obtaining Hgb A1c to screen for prediabetes/diabetes in patients with ischemic stroke or TIA. C As per AHA 2019 guidelines, consider obtaining screening for diabetes mellitus with testing of fasting plasma glucose, Hgb A1c, or an oral glucose tolerance test in all patients after AIS. Guide the choice of test and timing by clinical judgment and recognition that acute illness may temporarily perturb measures of plasma glucose. Recognize that Hgb A1c may be more accurate than other screening tests in the immediate post-event period. C Screening for obstructive sleep apnea: As per AHA 2021 guidelines: Consider obtaining evaluation for obstructive sleep apnea in patients with ischemic stroke or TIA. C Consider offering positive airway pressure (such as CPAP) to relieve sleep apnea and improve BP, sleepiness, and other apnea-related outcomes in patients with ischemic stroke or TIA and obstructive sleep apnea. C As per AHA 2019 guidelines, do not obtain routine screening for obstructive sleep apnea in patients with recent ischemic stroke. D Screening for central hypothyroidism: evaluate for central hypothyroidism in all patients with stroke, particularly in the presence of hypothyroid manifestations. B 4. Respiratory support Airway support: provide airway support and ventilatory assistance for the treatment of patients with acute stroke having decreased consciousness or having bulbar dysfunction causing compromise of the airway. B Supplemental oxygen: administer supplemental oxygen to maintain oxygen saturation > 94%. B Show 2 more https://web.pathway.md/diseases/recwd1RIpW03JSM4H 5/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Hyperbaric oxygen therapy: do not use hyperbaric oxygen therapy in patients with AIS except when caused by air embolization. D 5. Medical management Prehospital care: as per AHA 2019 guidelines, ensure the use of a stroke assessment tool by first aid providers including emergency medical services dispatch personnel. B Show 4 more Intravenous alteplase, timing: As per ASA/AHA 2019 guidelines, initiate treatment as quickly as possible in patients eligible for IV alteplase because the benefit of therapy is time-dependent. A Show 9 more As per ACEP 2015 guidelines, administer IV alteplase with a goal to improve functional outcomes in selected patients with AIS within 3 hours after symptom onset at institutions where systems are in place to safely administer the medication. Take the increased risk of symptomatic intracerebral hemorrhage into consideration when deciding whether to administer IV alteplase in patients with AIS. B Show 2 more Intravenous alteplase (pre-administration evaluation): Assess blood glucose levels before administering IV alteplase since hypoglycemia and hyperglycemia may mimic acute stroke presentations. B . Do not administer IV alteplase for nonvascular conditions. B Obtain baseline ECG B and troponin assessment not delaying initiation of IV alteplase in patients presenting with AIS. B Landmark trials: NINDS In patients with ischemic stroke, tPA was superior to placebo with respect to death at 90 days. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995 Dec 14. Intravenous alteplase (concomitant thrombectomy): Administer IV alteplase in patients eligible for IV alteplase even if mechanical thrombectomy is being considered. A Do not obtain observation after IV alteplase for the assessment of clinical response in patients under consideration for mechanical thrombectomy. D Intravenous alteplase, bleeding risk: As per ASA/AHA 2019 guidelines, avoid delaying urgent IV alteplase administration while waiting for hematologic or coagulation testing if there is no reason to suspect an abnormal test, https://web.pathway.md/diseases/recwd1RIpW03JSM4H 6/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway given the extremely low risk of unsuspected abnormal platelet counts or coagulation studies in a population. D Show 6 more As per ASA/AHA 2018 guidelines, do not administer IV alteplase in patients with AIS with platelets < 100, 000/mm , INR > 1.7, activated PTT > 40 sec, or PT > 15. D Show 9 more Intravenous alteplase (complications): Discuss the potential risks of IV alteplase administration during eligibility deliberation and weigh the risks against the anticipated benefits during decision-making. B Be prepared to treat potential emergent adverse effects including bleeding complications and angioedema causing partial airway obstruction in patients undergoing fibrinolytic therapy. B Intravenous alteplase (post-administration care): Maintain BP at < 180/105 mmHg for at least the first 24 hours after IV alteplase administration. B Insufficient evidence regarding the risk of antithrombotic therapy (other than IV aspirin) within the first 24 hours after treatment with IV alteplase (with or without mechanical thrombectomy). Consider initiating antithrombotic therapy in the presence of concomitant conditions for which such treatment given in the absence of IV alteplase is known to provide a substantial benefit or withholding such treatment is known to cause substantial risk. I Intravenous tenecteplase: As per ESO 2023 guidelines, consider administering tenecteplase 0.25 mg/kg as an alternative to alteplase 0.9 mg/kg in patients with AIS of < 4.5 hours duration eligible for IV thrombolysis. B Consider preferring tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg in these patients in light of safety and efficacy data and because tenecteplase can be administered with a single bolus rather than a 1-hour infusion. E Do not use tenecteplase at a dose of 0.40 mg/kg. B Show 4 more As per AHA 2019 guidelines, consider administering tenecteplase (single IV bolus of 0.25 mg/kg, maximum 25 mg) over IV alteplase in patients eligible for mechanical thrombectomy and not having contraindications to IV fibrinolysis. C Show 2 more Antiplatelet therapy: As per ESO 2022 guidelines: Consider initiating dual antiplatelet therapy in preference to single antiplatelet therapy in patients with ischemic stroke or TIA related to intracranial stenosis due to intracranial atherosclerotic disease. C Insufficient evidence to recommend an additional infusion of glycoprotein IIb/IIIa inhibitors after initial mechanical thrombectomy in patients with AIS due to an intracranial atherosclerotic disease-related intracranial arterial occlusion. I As per AHA 2021 guidelines, initiate antiplatelet therapy over oral anticoagulation to reduce the risk of recurrent ischemic stroke and other cardiovascular events while minimizing the risk of https://web.pathway.md/diseases/recwd1RIpW03JSM4H 7/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway bleeding in patients with non-cardioembolic ischemic stroke or TIA. A Show 5 more As per AHA 2019 guidelines, initiate aspirin in patients with AIS within 24-48 hours after onset. Consider delaying aspirin initiation until 24 hours later in patients treated with IV alteplase, but consider initiating in the presence of concomitant conditions for which such treatment given in the absence of IV alteplase is known to provide a substantial benefit or withholding such treatment is known to cause substantial risk. A Show 8 more Updated evidence: RESCUE BT In patients with stroke and proximal intracranial large vessel occlusion presenting < 24 hours of time last known well, tirofiban was not superior to placebo with respect to disability level, mRS score, at day 90. RESCUE BT Trial Investigators et al. JAMA. 2022 Aug 9. Anticoagulant therapy: As per ESO 2022 guidelines, do not use oral anticoagulation over aspirin, unless there is another formal indication for it, in patients with ischemic stroke or TIA due to high-grade stenosis related to intracranial atherosclerotic disease. D As per AHA 2019 guidelines, insufficient evidence to recommend urgent anticoagulation in patients with severe stenosis of an internal carotid artery ipsilateral to an ischemic stroke. I Show 6 more Updated evidence: ARAIS In adult patients with acute ischemic stroke who were assigned within 4.5 hours of symptom onset, argatroban plus alteplase was not superior to alteplase alone with respect to excellent functional outcome at day 90. Hui-Sheng Chen et al. JAMA. 2023 Feb 9. Management of blood pressure: As per ESO 2022 guidelines, insufficient evidence to recommend permissive or induced hypertension over conventional BP management (target normotension) during the acute phase in patients with AIS or TIA related to high-grade intracranial atherosclerosis causing severe hemodynamic compromise. I As per AHA 2021 guidelines, consider initiating thiazide diuretics, ACEIs, or ARBs to lower BP and reduce recurrent stroke risk in patients with hypertension experiencing a stroke or TIA. B Show 3 more https://web.pathway.md/diseases/recwd1RIpW03JSM4H 8/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway As per AHA 2019 guidelines, correct hypotension and hypovolemia to maintain systemic perfusion levels necessary to support organ function. B Show 9 more Management of glucose levels: As per AHA 2019 guidelines: Treat hypoglycemia (blood glucose < 60 mg/dL) in patients with AIS. B Consider treating hyperglycemia to achieve blood glucose levels of 140-180 mg/dL and obtaining close monitoring to prevent hypoglycemia in patients with AIS since persistent in- hospital hyperglycemia during the first 24 hours after AIS is associated with worse outcomes. C As per ESO 2017 guidelines, avoid administering IV insulin routinely to achieve tight glycemic control in order to improve functional outcome, survival, or infarct growth in patients with AIS. D Management of temperature: As per ESO 2019 guidelines, identify and treat sources of hyperthermia (temperature > 38 C), and administer antipyretic medications to lower temperature in hyperthermic patients with stroke. B Show 2 more As per AHA 2015 guidelines, insufficient evidence to recommend treating hyperthermia in order to improve functional outcome and/or survival in patients with AIS and hyperthermia. I Show 2 more Management of cerebral edema (general principles): Recognize that patients with large territorial cerebral and cerebellar infarctions are at high risk for developing brain swelling and herniation. Discuss care options and possible outcomes quickly with patients (if possible) and family or next of kin. Ensure that medical professionals and caregivers ascertain and include patient-centered preferences in shared decision-making, especially during prognosis formation and when considering interventions or limitations in care. B Underake measures to lessen the risk of swelling and obtain close monitoring for signs of neurological worsening during the first days after stroke. Consider transferring patients at risk for malignant brain swelling early to an institution with appropriate neurosurgical expertise. B Management of cerebral edema (medical management): consider administering osmotic therapy in patients with clinical deterioration from cerebral edema associated with cerebral infarction. C Show 3 more Management of cerebral edema (surgical management, supratentorial infarction): Consider performing decompressive craniectomy in patients with supratentorial infarction and decreased level of consciousness attributed to brain swelling. B Consider performing decompressive craniectomy with dural expansion in patients, either aged 60 years B or > 60 years, deteriorating neurologically within 48 hours from brain swelling associated with unilateral middle cerebral artery infarction despite medical therapy. C https://web.pathway.md/diseases/recwd1RIpW03JSM4H 9/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Management of cerebral edema (surgical management, cerebellar infarction): perform ventriculostomy for the treatment of obstructive hydrocephalus after cerebellar infarction. Consider performing concomitant or subsequent decompressive craniectomy based on factors such as the size of the infarction, neurological condition, degree of brainstem compression, and effectiveness of medical management. B Show 2 more Management of seizures: As per AHA 2019 guidelines: Manage recurrent seizures after stroke similarly to seizures occurring with other acute neurological conditions, with the choice of antiseizure drugs based on specific patient characteristics. B Do not administer prophylactic antiseizure drugs. D As per ESO 2017 guidelines, avoid administering primary or secondary antiepileptic drug prophylaxis to prevent acute symptomatic seizures after stroke. D Show 5 more Management of dyslipidemia: As per ESO 2022 guidelines, consider ensuring aggressive vascular risk factor control, including lipid management and lifestyle changes (increased physical activity), in order to improve outcomes in patients with ischemic stroke or TIA related to intracranial atherosclerotic disease. C As per AHA 2021 guidelines, initiate atorvastatin 80 mg/day to reduce the risk of stroke recurrence in patients with ischemic stroke with no known coronary heart disease, no major cardiac sources of embolism, and LDL cholesterol > 100 mg/dL. A Show 5 more As per AHA 2019 guidelines, consider continuing statin therapy during the acute period in patients already taking statins at the time of onset of ischemic stroke. C Show 15 more Therapies with no evidence for benefit: Do not use the following therapies for the treatment of patients with AIS: hemodilution by volume expansion high-dose albumin vasodilatory agents, such as pentoxifylline. D Avoid using devices for mechanical augmentation of cerebral blood flow in patients with AIS. D Palliative care: consider referring patients and families with stroke to palliative care resources as appropriate. C 6. Inpatient care Thromboprophylaxis, intermittent pneumatic compression: https://web.pathway.md/diseases/recwd1RIpW03JSM4H 10/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway As per ASA/AHA 2019 guidelines, offer intermittent pneumatic compression, if not contraindicated, in addition to routine care (aspirin and hydration) to reduce the risk of deep vein thrombosis in immobile patients with stroke. B As per ESO 2016 guidelines: Offer intermittent pneumatic compression (thigh-length, sequential) in immobile patients with AIS. B Do not use intermittent pneumatic compression in patients with open wounds on the legs. Be cautious when using in patients with existing deep vein thrombosis, HF, severe peripheral vascular disease, or confusion where attempts to mobilize when unsupervised could lead to falls and injury. D Thromboprophylaxis, anticoagulation: As per ASA/AHA 2019 guidelines: Insufficient evidence to support the use of prophylactic-dose SC heparin (UFH or LMWH) in patients with AIS. I Insufficient evidence to recommend prophylactic-dose LMWH in preference to prophylactic- dose UFH when prophylactic anticoagulation is used. I As per ESO 2016 guidelines: Consider administering prophylactic anticoagulation with UFH (5,000 U BID or TID) or LMWH or heparinoids in immobile patients with AIS if the benefits of reducing the risk of VTE is high enough to offset the increased risks of intracranial and extracranial bleeding associated with their use. C Consider administering LMWH or heparinoids over UFH for prophylactic anticoagulation because of their greater reduction in risk of deep vein thrombosis, the greater convenience, reduced staff costs, and patient comfort associated single daily dose versus multiple daily injections, while weighing these advantages against the higher risk of extracranial bleeding, higher drug costs, and risks in elderly patients with poor renal function. C Thromboprophylaxis, compression stockings: As per ASA/AHA 2019 guidelines, do not use elastic compression stockings in patients with AIS. D As per ESO 2016 guidelines, do not use graduated compression stockings in patients with AIS. D Antibiotic prophylaxis: avoid using routine prophylactic antibiotics in patients with ischemic stroke. D Pressure ulcer prophylaxis: obtain regular skin assessments with objective scales of risk (such as the Braden scale) during hospitalization and inpatient rehabilitation. B Show 2 more Nutritional support: start enteral diet within 7 days of admission after an acute stroke. B Show 2 more https://web.pathway.md/diseases/recwd1RIpW03JSM4H 11/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Indwelling bladder catheters: do not place indwelling bladder catheters routinely because of the associated risk of catheter-associated UTIs. D 7. Nonpharmacologic interventions Dietary modifications: Consider advising to follow a Mediterranean-type diet, typically with an emphasis on monounsaturated fat, plant-based foods, and fish consumption, with either high extra virgin olive oil or nut supplementation, in preference to a low-fat diet, to reduce the risk of recurrent stroke in patients with stroke and TIA. C Consider advising to reduce the sodium intake by at least 1 g/day sodium (2.5 g/day salt) to reduce the risk of CVD events, including stroke, in patients with stroke or TIA and hypertension. C Physical activity: advise practicing at least moderate-intensity aerobic activity for a minimum of 10 minutes 4 times weekly or vigorous-intensity aerobic activity for a minimum of 20 minutes twice weekly to lower the risk of recurrent stroke and the composite cardiovascular endpoint of recurrent stroke, myocardial infarction, or vascular death in patients with stroke or TIA capable of physical activity. B Show 3 more Weight loss: calculate BMI at the time of the event and annually thereafter to screen for and to classify obesity in patients with ischemic stroke or atherosclerotic CVD. B Show 2 more Smoking cessation: As per AHA 2021 guidelines, offer counseling with or without pharmacotherapy (nicotine replacement, bupropion, or varenicline) to assist in quitting smoking in smoker patients with stroke or TIA. A Show 2 more As per AHA 2019 guidelines, provide in-hospital high-intensity behavioral interventions to promote smoking cessation in smoker patients with AIS. Offer nicotine replacement therapy in patients receiving in-hospital high-intensity behavioral interventions. A Show 3 more Alcohol consumption: advise eliminating or reducing consumption of alcohol to reduce stroke risk in patients with ischemic stroke or TIA consuming excess alcohol (> 2 alcoholic drinks a day for males or > 1 alcoholic drink a day for females). B Substance use cessation: Provide counseling and advise stopping using stimulants in patients with stroke or TIA using stimulants (such as amphetamines, amphetamine derivatives, cocaine, or khat) and patients with infective endocarditis in the context of IV drug use. B Offer specialized services to help manage dependency in patients with stroke or TIA having a substance use disorder (drugs or alcohol). B https://web.pathway.md/diseases/recwd1RIpW03JSM4H 12/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Head positioning: insufficient evidence to recommend flat-head positioning early after hospitalization for stroke. I 8. Therapeutic procedures Indications for thrombectomy (0-6 hours from onset): Perform mechanical thrombectomy with a stent retriever in patients meeting all the following criteria: age 18 years pre-stroke mRS score of 0-1 causative occlusion of the internal carotid artery or middle cerebral artery segment 1 (M1) NIHSS score of 6 alberta Stroke Program Early CT Score of 6 treatment can be initiated (groin puncture) within 6 hours of symptom onset. A Show 4 more Indications for thrombectomy (6-24 hours from onset): Perform mechanical thrombectomy in selected patients with AIS with large vessel occlusion in the anterior circulation within 6-16 hours of last known normal meeting other DAWN or DEFUSE 3 eligibility criteria. A Consider performing mechanical thrombectomy in selected patients with AIS with large vessel occlusion in the anterior circulation within 16-24 hours of last known normal meeting other DAWN eligibility criteria. C Technical considerations for thrombectomy: strive to achieve a mTICI grade 2b/3 angiographic result as the technical goal of thrombectomy to maximize the probability of a good functional clinical outcome. Attempt achieving reperfusion to mTICI grade 2b/3 as early as possible within the therapeutic window to ensure benefit. A Proceed to evaluation and treatment as rapidly as possible in the 6-24-hour thombectomy window to ensure access to treatment for the greatest proportion of patients. B Show 5 more Intracranial angioplasty/stenting: As per ESO 2022 guidelines: Do not perform angioplasty and/or stenting, in addition to best medical treatment, as first-line treatment in patients with ischemic stroke or TIA related to high-grade stenosis due to intracranial atherosclerotic disease. D Insufficient evidence to recommend angioplasty and/or stenting after initial mechanical thrombectomy in patients with AIS due to an intracranial atherosclerotic disease-related intracranial arterial occlusion. I As per AHA 2021 guidelines, insufficient evidence to recommend angioplasty alone or stent placement to prevent ischemic stroke in the territory of the stenotic artery in patients with severe stenosis (70-99%) of a major intracranial artery and actively progressing symptoms or recurrent https://web.pathway.md/diseases/recwd1RIpW03JSM4H 13/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway TIA or stroke after institution of aspirin and clopidogrel therapy, achievement of systolic BP < 140 mmHg, and high-intensity statin therapy (so-called medical failures). I Show 2 more Carotid artery revascularization: As per AHA 2021 guidelines, perform carotid endarterectomy to reduce the risk of future stroke in patients with non-disabling ischemic stroke or TIA within the past 6 months and ipsilateral severe (70-99%) carotid artery stenosis, provided the perioperative morbidity and mortality risk is < 6%. A Show 9 more As per AHA 2019 guidelines, insufficient evidence to recommend emergent or urgent carotid endarterectomy/carotid angioplasty and stenting when clinical indicators or brain imaging suggests a small infarct core with large territory at risk (such as penumbra), compromised by inadequate flow from critical carotid stenosis or occlusion, or in the case of acute neurological deficit after carotid endarterectomy with suspected acute thrombosis of the surgical site. I Show 2 more Vertebral artery revascularization: insufficient evidence to recommend stenting I or open surgical procedures including vertebral endarterectomy in patients with ischemic stroke or TIA and extracranial vertebral artery stenosis having symptoms despite optimal medical treatment. I Ischemic preconditioning: considering performing ischemic preconditioning as an adjuvant to best medical treatment in patients with ischemic stroke or TIA related to high-grade stenosis due to intracranial atherosclerotic disease. Consider enrolling patients in a dedicated RCT whenever possible. C Intra-arterial thrombolysis: perform mechanical thrombectomy with stent retrievers over intra- arterial fibrinolysis as first-line therapy. B Show 2 more Laser therapy: do not perform transcranial near-infrared laser therapy for the treatment of AIS. D Ultrasound-enhanced systemic thrombolysis: do not use sonothrombolysis as adjuvant therapy with IV fibrinolysis. D 9. Surgical interventions Decompressive craniectomy (supratentorial infarction): Consider performing decompressive craniectomy in patients with supratentorial infarction and decreased level of consciousness attributed to brain swelling. B Consider performing decompressive craniectomy with dural expansion in patients, either aged 60 years B or > 60 years, deteriorating neurologically within 48 hours from brain swelling associated with unilateral middle cerebral artery infarction despite medical therapy. C Decompressive craniectomy (cerebellar infarction): perform ventriculostomy for the treatment of obstructive hydrocephalus after cerebellar infarction. Consider performing concomitant or subsequent decompressive craniectomy based on factors such as the size of the infarction, https://web.pathway.md/diseases/recwd1RIpW03JSM4H 14/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway neurological condition, degree of brainstem compression, and effectiveness of medical management. B Show 2 more Extracranial-intracranial bypass surgery: Do not perform extracranial-intracranial bypass surgery in patients with stroke or TIA attributable to 50-99% stenosis or occlusion of a major intracranial artery. D Do not perform extracranial-intracranial bypass surgery in patients with a recent (within 120 days) TIA or ischemic stroke ipsilateral to atherosclerotic stenosis or occlusion of the middle cerebral or carotid artery. D 10. Specific circumstances Female patients (lifestyle modifications): Advise a healthy lifestyle consisting of the following for primary stroke prevention in patients with cardiovascular risk factors: regular physical activity moderate alcohol consumption (< 1 drink/day for nonpregnant females) abstention from cigarette smoking diet rich in fruits, vegetables, grains, nuts, and olive oil, and low in saturated fat (such as the DASH diet). B Advise lifestyle interventions focusing on diet and exercise for primary stroke prevention in individuals at high risk for stroke. B Female patients (use of oral contraceptives): recognize that oral contraceptives may be harmful in patients with additional risk factors (such as cigarette smoking, history of thromboembolic events). B Show 3 more Female patients, use of postmenopausal hormone therapy: As per ESO 2022 guidelines, avoid using HRT to reduce the risk of ischemic stroke or mortality from acute stroke in postmenopausal females. D As per ASA/AHA 2014 guidelines: Do not use hormone therapy (conjugated equine estrogen with or without medroxyprogesterone) for primary or secondary prevention of stroke in postmenopausal females. D Do not use selective estrogen receptor modulators, such as raloxifene, tamoxifen, or tibolone, for primary prevention of stroke. D Female patients (secondary prevention): screen female patients with asymptomatic carotid stenosis for other treatable risk factors for stroke and institute appropriate lifestyle changes and medical therapies. B Show 8 more https://web.pathway.md/diseases/recwd1RIpW03JSM4H 15/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Female patients (patients with migraine with aura): Consider offering treatment to reduce migraine frequency because there is an association between higher migraine frequency and stroke risk, although evidence is lacking that this treatment reduces the risk of first stroke. C Consider advising smoking cessation in patients with migraine with aura because of the increased stroke risk. C Female patients (patients with atrial fibrillation): use risk stratification tools in AF accounting for age- and sex-specific differences in the incidence of stroke. A Show 4 more Female patients (patients with CVT, nonpregnant): obtain a CBC, chemistry panel, PT, and activated PTT in patients with suspected cerebral venous thrombosis. B Show 4 more Female patients (patients with CVT, pregnant): continue LMWH in full anticoagulant doses throughout pregnancy, and LMWH or vitamin K antagonist with a target INR of 2.0-3.0 for 6 weeks postpartum (for a total minimum duration of therapy of 6 months) in patients with cerebral venous thrombosis during pregnancy. B Show 3 more Female patients (stroke during menstruation): Insufficient evidence to recommend IV thrombolysis in female patients with ischemic stroke during menstruation. Consider administering IV alteplase after appropriate assessment of the benefit/risk profile on an individual basis in female patients with AIS during menstruation, otherwise meeting eligibility criteria. E Pregnant patients, IV alteplase: As per ESO 2022 guidelines: Insufficient evidence to recommend IV thrombolysis in pregnant patients with AIS. I Consider administering IV alteplase after appropriate assessment of the benefit/risk profile on an individual basis in pregnant patients with acute disabling ischemic stroke, otherwise meeting eligibility criteria. E As per ASA/AHA 2018 guidelines: Consider administering IV alteplase in pregnant patients with AIS when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding. C Insufficient evidence regarding the safety and efficacy of IV alteplase in the early postpartum period (such as < 14 days after delivery). I Pregnant patients (mechanical thrombectomy): Insufficient evidence to recommend mechanical thrombectomy in pregnant patients with AIS. I Consider performing mechanical thrombectomy after appropriate assessment of the benefit/risk profile on an individual basis in pregnant patients with AIS and large vessel occlusion, otherwise https://web.pathway.md/diseases/recwd1RIpW03JSM4H 16/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway meeting eligibility criteria. Consider preferring mechanical thrombectomy alone, if available, over IV thrombolysis or bridging therapy (IV thrombolysis with mechanical thrombectomy) in pregnant patients with AIS related to large vessel occlusion. E Pregnant patients (anticoagulation therapy): Consider the following options for pregnant women with ischemic stroke or TIA and high-risk thromboembolic conditions such as hypercoagulable state or mechanical heart valves: adjusted dose UFH throughout pregnancy, for example, a subcutaneous dose every 12 hours with monitoring of activated PTT; adjusted-dose LMWH with monitoring of anti-factor Xa throughout pregnancy; or UFH or LMWH until week 13, followed by warfarin until the middle of the third trimester and reinstatement of UFH or LMWH until delivery. C Consider pregnant women with stroke or TIA for treatment with UFH or LMWH throughout the first trimester, followed by low-dose aspirin for the remainder of the pregnancy in the absence of a high-risk thromboembolic condition. C Pregnant patients (prevention of preeclampsia): initiate low-dose aspirin from the 12th week of gestation until delivery in pregnant patients with chronic primary or secondary hypertension or previous pregnancy-related hypertension. A Show 6 more Pregnant patients (lipid-lowering therapy): Advise using a reliable form of contraception in sexually active females of childbearing age treated with statin therapy. B Advise stopping statins 1-2 months before attempting pregnancy in females of childbearing age with hypercholesterolemia, or as soon as the pregnancy is discovered. B Postpartum patients: insufficient evidence to recommend IV thrombolysis in postpartum patients with AIS. I Show 3 more