What are the guideline sources, guidelines and references for Acute ischemic stroke ?
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 Patients with diabetes mellitus: As per ADA 2023 guidelines, consider offering pioglitazone to lower the risk of stroke or myocardial infarction in patients with a history of stroke and evidence of insulin resistance and prediabetes, balancing the benefits with the increased risk of weight gain, edema, and fracture. B Consider offering lower doses to mitigate the risk of adverse effects. C As per AHA 2021 guidelines, " consider advising lifestyle optimization (healthy diet, regular physical activity, and smoking cessation) to prevent the progression of prediabetes to diabetes in patients with ischemic stroke or TIA and prediabetes. B Show 6 more Patients with renal disease: administer IV alteplase in patients with end-stage renal disease on hemodialysis and normal activated PTT. B Patients with rercent traumatic injury: do not administer IV alteplase in patients with AIS with recent severe head trauma (within 3 months). D Show 2 more https://web.pathway.md/diseases/recwd1RIpW03JSM4H 17/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Patients with a history of recent surgery: Avoid administering IV alteplase in patients with AIS and a history of intracranial/spinal surgery within the prior 3 months. D Consider administering IV alteplase in carefully selected patients presenting with AIS undergone major surgery in the preceding 14 days, but weigh the potential increased risk of surgical-site hemorrhage against the anticipated benefits of reduced stroke-related neurological deficits. C Patients with a history of recent ischemic stroke: avoid administering IV alteplase in patients presenting with AIS with a prior ischemic stroke within 3 months. D Patients with hyperdense MCA sign: consider administering IV alteplase in patients with a hyperdense middle cerebral artery sign. C Patients with severe hypoattenuation lesions: insufficient evidence to recommend a threshold of hypoattenuation severity or extent affecting treatment response to alteplase. Do not administer IV alteplase in patients with extensive regions of clear hypoattenuation on CT. Recognize that these patients have a poor prognosis despite IV alteplase, and severe hypoattenuation defined as obvious hypodensity represents irreversible injury. I Patients with embolic stroke of undetermined source: do not use direct OACs D or ticagrelor to reduce the risk of secondary stroke in patients with embolic stroke of undetermined source. D Patients with hemorrhagic transformation: consider initiating or continuing antiplatelet or anticoagulation therapy depending on the specific clinical scenario and underlying indication in patients with AIS and hemorrhagic transformation. C Patients with procedural stroke: consider administering IV alteplase for the treatment of AIS complications of cardiac or cerebral angiographic procedures, depending on the usual eligibility criteria. B Patients with drug-associated ischemic stroke: recognize that illicit drug use may be a contributing factor to incident stroke. Consider administering IV alteplase in instances of illicit drug use-associated AIS in patients with no other exclusions. B Patients with cerebral venous sinus thrombosis: Consider anticoagulation for patients with acute cerebral venous sinus thrombosis. C Consider anticoagulation for at least 3 months, followed by antiplatelet therapy in the absence of trial data to define the optimal duration of anticoagulation for acute cerebral venous sinus thrombosis. C Patients with neurological deficits: consider administering IV alteplase in patients with stroke with severe neurological deficits and a high likelihood of morbidity and mortality, to outweigh the anticipated risk of intracerebral hemorrhage secondary to thrombolysis, because of the increased risk of intracerebral hemorrhage in this group of patients. C Patients with disability or impairement: consider administering IV alteplase in patients with preexisting disability (Modified Rankin Score 2), taking into account relevant factors including quality of life, social support, place of residence, need for a caregiver, patients and family preferences, and goals of care. C https://web.pathway.md/diseases/recwd1RIpW03JSM4H 18/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Show 2 more Patients with inherited thrombophilias: Consider initiating antiplatelet therapy to reduce the risk of recurrent stroke or TIA in patients with ischemic stroke or TIA of unknown source despite thorough diagnostic evaluation, no other thrombotic history, and having any of the following: prothrombin 20210A mutation activated protein C resistance elevated factor VIII levels protein C deficiency protein S deficiency antithrombin III deficiency. C Patients with antiphospholipid syndrome: initiate antiplatelet therapy alone to reduce the risk of recurrent stroke in patients with ischemic stroke or TIA having an isolated antiphospholipid antibody but not fulfilling the criteria for antiphospholipid syndrome. B Show 3 more Patients with hyperhomocysteinemia: Do not initiate folate, vitamin B6, or vitamin B12 supplementation for the prevention of subsequent stroke in patients with ischemic stroke or TIA and hyperhomocysteinemia. D Offer a low-methionine, cysteine-enhanced diet and initiate vitamin B6, vitamin B12, and folate supplementation to reduce plasma homocysteine to population normal levels and thereby reduce the risk of recurrent ischemic stroke in patients with ischemic stroke or TIA and cystathionine -synthase deficiency. B Patients with malignancy: As per AHA 2021 guidelines, consider initiating anticoagulation with direct OACs in preference to warfarin for the prevention of stroke in patients with ischemic stroke or TIA in the setting of AF and cancer. C As per AHA 2018 guidelines, insufficient evidence regarding the safety and efficacy of IV alteplase in patients with current malignancy. I Patients with sickle cell disease (management): consider administering IV alteplase in adult patients with known sickle cell disease presenting with an AIS. C Patients with sickle cell disease (secondary prevention): Administer chronic blood transfusions to reduce Hgb S to < 30% of total Hgb for the prevention of recurrent ischemic stroke in patients with sickle cell disease and prior ischemic stroke or TIA. B Consider initiating hydroxyurea for the prevention of recurrent ischemic stroke in patients with sickle cell disease with prior ischemic stroke or TIA, if transfusion therapy is not available or practical. C Patients with autoimmune vasculitis: initiate immediate oral high-dose corticosteroids to reduce recurrent stroke risk in patients with ischemic stroke or TIA and symptoms attributed to giant cell arteritis. B https://web.pathway.md/diseases/recwd1RIpW03JSM4H 19/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Show 3 more Patients with infectious vasculitis: Treat the underlying infectious etiology (such as VZV, cerebral vasculitis, neurosyphilis, or bacterial meningitis) to reduce the risk of stroke in patients with ischemic stroke or TIA and infectious vasculitis. B Consider initiating daily aspirin plus combined ART to reduce the risk of recurrent stroke in patients with ischemic stroke or TIA in the context of human immunodeficiency virus vasculopathy. C Patients with Fabry disease: insufficient evidence regarding the role of agalsidase alfa or agalsidase beta in preventing recurrent stroke or TIA in patients with ischemic stroke or TIA and Anderson-Fabry disease. I Patients with carotid artery stenosis: initiate intensive medical therapy with antiplatelet therapy, lipid-lowering therapy, and antihypertensive therapy to reduce the risk of stroke in patients with TIA or stroke and carotid artery stenosis. A Show 11 more Patients with vertebral artery stenosis: Initiate intensive medical therapy (antiplatelet therapy, lipid-lowering, BP control) to reduce stroke risk in patients with recently symptomatic extracranial vertebral artery stenosis. A Insufficient evidence to recommend stenting I or open surgical procedures, including vertebral endarterectomy and vertebral artery transposition, in patients with ischemic stroke or TIA and extracranial vertebral artery stenosis having symptoms despite optimal medical treatment. I Patients with carotid or vertebral artery dissection: As per AHA 2021 guidelines, initiate antithrombotic therapy for at least 3 months to prevent recurrent stroke or TIA in patients with ischemic stroke or TIA after an extracranial carotid or vertebral arterial dissection. B Show 2 more As per AHA 2019 guidelines: Consider initiating either antiplatelet or anticoagulant therapy for 3-6 months in patients with AIS and extracranial carotid or vertebral arterial dissection. C Insufficient evidence to recommend extracranial endovascular therapy (stenting) in patients with AIS and extracranial carotid or extracranial vertebral arterial dissection experiencing definite recurrent cerebral ischemic events despite medical therapy. I Patients with aortic arch atherosclerosis: Initiate intensive lipid management with an LDL-C target of < 70 mg/dL to prevent recurrent stroke in patients with stroke or TIA and evidence of an aortic arch atheroma. B Initiate antiplatelet therapy to prevent recurrent stroke in patients with stroke or TIA and evidence of an aortic arch atheroma. B Patients with aortic arch dissection: do not administer IV alteplase in patients with AIS known or suspected to be associated with aortic arch dissection. D https://web.pathway.md/diseases/recwd1RIpW03JSM4H 20/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Patients with intracranial aneurysms: consider administering IV alteplase in patients presenting with AIS known to harbor a small or moderate-sized, unruptured, and unsecured intracranial aneurysm. C Show 2 more Patients with intracranial neoplasms: Consider administering IV alteplase in patients with AIS harboring an extra-axial intracranial neoplasm. C Avoid administering IV alteplase in patients with AIS harboring an intra-axial intracranial neoplasm. D Patients with Moyamoya disease: Consider initiating antiplatelet therapy, typically aspirin monotherapy, for the prevention of ischemic stroke or TIA in patients with Moyamoya disease and a history of ischemic stroke or TIA. C Consider performing surgical revascularization with direct or indirect extracranial-intracranial bypass for the prevention of ischemic stroke or TIA in patients with Moyamoya disease and a history of ischemic stroke or TIA. C Patients with small vessel disease: insufficient evidence to support the use of cilostazol for secondary prevention of stroke in patients with ischemic stroke related to small vessel disease. I Patients with carotid web: Initiate antiplatelet therapy to prevent recurrent ischemic stroke or TIA in patients with carotid web in the distribution of ischemic stroke and TIA without other attributable causes of stroke. B Consider performing carotid stenting or carotid endarterectomy to prevent recurrent ischemic stroke in patients with carotid web in the distribution of ischemic stroke refractory to medical management with no other attributable cause of stroke despite comprehensive workup. C Patients with fibromuscular dysplasia: initiate antiplatelet therapy, control BP control, and offer lifestyle modifications for the prevention of future ischemic events in patients with a history of ischemic stroke or TIA and FMD without other attributable causes. B Show 2 more Patients with vertebrobasilar dolichoectasia: consider initiating antiplatelet or anticoagulant therapy for the prevention of recurrent ischemic events in patients with a history of ischemic stroke or TIA and vertebrobasilar dolichoectasia without other attributable causes. C Patients with atrial fibrillation, anticoagulation therapy: As per ASA/AHA 2021 guidelines, initiate oral anticoagulation, such as apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin, to reduce the risk of recurrent stroke in patients with stroke or TIA and nonvalvular AF. A Initiate oral anticoagulation to reduce the risk of recurrent stroke regardless of the pattern of AF, i.e. paroxysmal, persistent, or permanent. B Show 7 more As per ASA/AHA 2019 guidelines: Consider initiating oral anticoagulation between 4-14 days after the onset of neurological symptoms in most patients with AIS and AF. C https://web.pathway.md/diseases/recwd1RIpW03JSM4H 21/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Insufficient evidence to support adding antiplatelet therapy to OACs for purposes of reducing the risk of ischemic cardiovascular and cerebrovascular events in patients with a history of ischemic stroke, AF, and coronary artery disease. Consider initiating dual antiplatelet/oral anticoagulation in patients with unstable angina and coronary artery stenting. I Patients with atrial fibrillation (LAA closure): consider performing percutaneous closure of the LA appendage with the Watchman device to reduce the risk of recurrent stroke and bleeding in patients with stroke or TIA in the setting of nonvalvular AF having contraindications for lifelong anticoagulation but able to tolerate at least 45 days. C Patients with patent foramen ovale: decide between patent foramen ovale closure and medical management jointly with the patient, a cardiologist, and a neurologist taking into account the probability of a causal role for the patent foramen ovale in patients with a non-lacunar ischemic stroke of undetermined cause and a patent foramen ovale. B Show 3 more Patients with valvular heart disease (antithrombotic therapy): initiate warfarin to reduce the risk of recurrent stroke or TIA in patients with ischemic stroke or TIA and valvular AF (moderate-to- severe mitral stenosis or any mechanical heart valve). B Show 4 more Patients with valvular heart disease (valvular surgery): consider performing early surgery (during initial hospitalization before completion of a full therapeutic course of antibiotics) to reduce the risk of recurrent embolisms, if there is no evidence of ICH or extensive neurological damage, in patients with ischemic stroke or TIA and infective endocarditis presenting with recurrent emboli and persistent vegetations despite appropriate antibiotic therapy. C Show 4 more Patients with myocardial infarction: Consider administering IV alteplase at the dose appropriate for cerebral ischemia, followed by percutaneous coronary angioplasty and stenting if indicated, in patients presenting with concurrent AIS and acute myocardial infarction. C Consider administering IV alteplase in patients presenting with AIS and a history of recent myocardial infarction in the past 3 months, if the recent myocardial infarction was non-STEMI or STEMI involving the right, inferior, C or left anterior myocardium. C Patients with intracardiac thrombi: As per AHA 2021 guidelines, consider obtaining advanced cardiac imaging (such as contrast- enhanced echocardiography or cardiac MRI) to assess for the presence of LV thrombus in patients with stroke or TIA in the setting of acute myocardial infarction. C Show 3 more As per AHA 2018 guidelines: Consider administering IV alteplase in patients with a known LA or ventricular thrombus major AIS likely to produce severe disability. C Insufficient evidence to recommend IV alteplase administration in patients with a known LA or ventricular thrombus presenting with moderate AIS likely to produce mild disability. I https://web.pathway.md/diseases/recwd1RIpW03JSM4H 22/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Patients with congenital heart disease: Initiate anticoagulation with warfarin to reduce the risk of recurrent stroke or TIA in patients with ischemic stroke or TIA and Fontan palliation. B Consider initiating anticoagulation with warfarin to reduce the risk of recurrent stroke or TIA in patients with cyanotic congenital heart disease and other complex lesions and ischemic stroke or TIA of presumed cardioembolic origin. C Patients with cardiomyopathy: initiate anticoagulation with warfarin for at least 3 months to reduce the risk of recurrent stroke or TIA in patients with ischemic stroke or TIA and LA or LA appendage thrombus in the setting of ischemic, non-ischemic, or restrictive cardiomyopathy and LV dysfunction. B Show 4 more Patients with cardiac tumors: As per AHA 2021 guidelines, consider performing tumor resection to reduce the risk of recurrent stroke in patients with stroke or TIA with a left-sided cardiac tumor. C As per AHA 2018 guidelines: Consider administering IV alteplase in patients with cardiac myxoma and major AIS likely to produce severe disability. C Consider administering IV alteplase in patients with papillary fibroelastoma presenting with major AIS likely to produce severe disability. C Patients with infective endocarditis: do not administer IV alteplase in patients with AIS and symptoms consistent with infective endocarditis because of the increased risk of ICH. D Patients with acute pericarditis: Consider administering IV alteplase in patients with acute pericarditis and major AIS likely to produce severe disability. C Insufficient evidence to recommend administering IV alteplase in patients presenting with acute pericarditis and moderate AIS likely to produce mild disability. I 11. Preventative measures Primary prevention (statin therapy): initiate statins for primary prevention of CVDs in 40-75 years old adults with 1 CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD risk 10%. B Show 2 more Primary prevention (antiplatelet therapy): insufficient to support the use of antiplatelet therapy to reduce the risk of major adverse cardiovascular events including ischemic stroke in patients with asymptomatic intracranial atherosclerosis. Secondary prevention (antiplatelet therapy): initiate aspirin 325 mg/day over warfarin to reduce the risk of recurrent ischemic stroke and vascular death in patients with stroke or TIA caused by 50-99% stenosis of a major intracranial artery. B https://web.pathway.md/diseases/recwd1RIpW03JSM4H 23/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Show 4 more Secondary prevention (health system-based interventions): implement voluntary hospital- based or outpatient-focused quality monitoring and improvement programs to improve short-term and long-term adherence to nationally accepted, evidence-based guidelines for secondary stroke prevention in patients with ischemic stroke or TIA. B Show 2 more Secondary prevention (behavioral changes): offer behavior change interventions targeting stroke literacy, lifestyle factors, and medication adherence to reduce cardiovascular events in patients with ischemic stroke or TIA. B Show 5 more 12. Follow-up and surveillance Rehabilitation, approach and timing: As per ASA/AHA 2019 guidelines, provide early rehabilitation in patients hospitalized for stroke in environments with organized, interprofessional stroke care. A Show 3 more As per DoD/VA 2019 guidelines, provide a team-based approach in an organized inpatient unit encompassing comprehensive rehabilitation in order to improve the likelihood of discharge to home after acute stroke. A Show 3 more Rehabilitation, motor therapy: As per ASA/AHA 2019 guidelines, insufficient evidence to support the use of fluoxetine or other SSRIs to enhance motor recovery. I Updated evidence: EFFECTS In adult patients with a clinical diagnosis of ischemic or intracerebral hemorrhage in the previous 2-15 days, fluoxetine was not superior to placebo with respect to physical function as measured by the stroke impact scale score. EFFECTS Trial Collaboration. Lancet Neurol. 2020 Aug. As per DoD/VA 2019 guidelines, offer task-specific practice ("task-oriented practice" or "repetitive task practice") for improving upper- and lower-extremity motor function, gait, posture, and activities of daily living. A Show 17 more Rehabilitation, evaluation for dysphagia: As per ESSD/ESO 2021 guidelines, obtain a formal dysphagia screening test (either water- swallow tests or multiple-consistency tests) as soon as possible after admission to prevent post- stroke pneumonia and decrease the risk of early mortality in all patients with acute stroke. B https://web.pathway.md/diseases/recwd1RIpW03JSM4H 24/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Show 2 more As per ASA/AHA 2019 guidelines, obtain dysphagia screening before the patient begins eating, drinking, or receiving oral medications to identify patients at increased risk for aspiration. B Consider obtaining dysphagia screening by speech-language pathologists or other trained healthcare providers. B Show 2 more Rehabilitation, dysphagia therapy, nutritional support: As per ESSD/ESO 2021 guidelines, do not administer any food or liquid items, including oral medications, until a dysphagia screening is obtained and swallowing is deemed safe. D Show 2 more As per DoD/VA 2019 guidelines, consider placing a gastrostomy tube to maintain optimal nutrition in patients with dysphagia in the post-acute phase of stroke requiring tube feeding. C Rehabilitation, dysphagia therapy, exercises: As per ESSD/ESO 2021 guidelines, consider offering behavioral swallowing exercises to rehabilitate swallowing function in patients with post-stroke dysphagia. Avoid limiting behavioral interventions to one specific maneuver or training but tailor the treatment to the specific swallowing impairment of the individual patient with post-stroke dysphagia based on a careful assessment of dysphagia. C As per DoD/VA 2019 guidelines, consider offering Shaker exercise or chin tuck against resistance exercises in addition to conventional dysphagia therapy. C Show 2 more Rehabilitation, dysphagia therapy, oral hygiene: As per ESSD/ESO 2021 guidelines, consider implementing oral health care interventions to reduce the risk of pneumonia in patients with stroke. C As per ASA/AHA 2019 guidelines, consider implementing oral hygiene protocols to reduce the risk of pneumonia after stroke. C Rehabilitation (dysphagia therapy, pharmacotherapy): offer pharmacological treatment of post- stroke dysphagia within clinical trial settings. B Show 3 more Rehabilitation, dysphagia therapy, electrical stimulation: As per ESSD/ESO 2021 guidelines, offer neurostimulation techniques in patients with post- stroke dysphagia within clinical trial settings. B Show 2 more As per DoD/VA 2019 guidelines, insufficient evidence to recommend for or against neuromuscular electrical stimulation or pharyngeal electrical stimulation for the treatment of dysphagia. I Rehabilitation (dysphagia therapy, acupuncture): consider offering acupuncture for the rehabilitation of swallowing function in patients with post-stroke dysphagia. C https://web.pathway.md/diseases/recwd1RIpW03JSM4H 25/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Rehabilitation (cognitive, speech, and sensory therapy): insufficient evidence to recommend for or against the use of any specific cognitive rehabilitation methodology or pharmacotherapy to improve cognitive outcomes. I Show 4 more Rehabilitation, depression and anxiety: As per ASA/AHA 2019 guidelines: Use a structured depression inventory to routinely screen for post-stroke depression. B Initiate antidepressants in the absence of contraindications and closely monitor to verify effectiveness in patients with post-stroke depression. B As per DoD/VA 2019 guidelines, insufficient evidence for or against the universal use of SSRIs or SNRIs for the prevention of post-stroke depression. I Show 6 more Rehabilitation (return to work): Insufficient evidence to recommend for or against any specific assessments or interventions regarding return to work. I Insufficient evidence to recommend for or against using any specific assessments or interventions to facilitate a return to driving. I 13. Quality improvement EMS services: Develop regional systems of stroke care consisting of healthcare facilities providing initial emergency care, including administration of IV alteplase, and centers capable of performing endovascular stroke treatment with comprehensive periprocedural care to which rapid transport can be arranged when appropriate. A Develop triage paradigms and protocols to ensure that patients with a known or suspected stroke are rapidly identified and assessed by use of a validated and standardized tool for stroke screening by emergency medical services leaders, in coordination with local, regional, and state agencies and in consultation with medical authorities and local experts. B Stroke centers/units: certify stroke centers by an independent external body. B Show 6 more Organization of care: develop, adopt, and adhere to care protocols reflecting current care guidelines as established by national and international professional organizations in all hospitals caring for stroke patients within a stroke system of care. B Show 4 more Telemedicine: implement teleradiology systems (approved by the US FDA) for timely review of brain imaging in patients with suspected acute stroke in sites without in-house imaging interpretation expertise. Recognize that teleradiology systems (approved by the US FDA) implemented within a telestroke network are effective in supporting rapid imaging interpretation in time for IV alteplase administration decision making. A https://web.pathway.md/diseases/recwd1RIpW03JSM4H 26/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Show 5 more Outcome measures: organize a multidisciplinary quality improvement committee in healthcare institutions to review and monitor stroke care quality benchmarks, indicators, evidence-based practices, and outcomes. Consider forming a clinical process improvement team and using a stroke care registry for such quality of care assurances. Consider using a data repository to identify the gaps or disparities in quality stroke care. Consider initiating specific interventions once the gaps have been identified to address these gaps or disparities. B Show 2 more Public health measures: design and implement public education programs focused on stroke systems and the need to seek emergency care in a rapid manner. B Health equity: assess and address social determinants of health (literacy level, language proficiency, medication affordability, food insecurity, housing, and transportation barriers) when managing stroke risk factors to reduce healthcare disparities. B Show 3 more References 1. William J Powers, Alejandro A Rabinstein, Teri Ackerson et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50 12):e344-e418. Open 2. Dawn O Kleindorfer, Amytis Towfighi, Seemant Chaturvedi et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52 7):e364-e467. Open 3. George Ntaios, Tomasz Dziedzic, Patrik Michel et al. European Stroke Organisation ESO guidelines for the management of temperature in patients with acute ischemic stroke. Int J Stroke. 2015 Aug;10 6 941 9. Open 4. Blanca Fuentes, George Ntaios, Jukka Putaala et al. European Stroke Organisation ESO guidelines on glycaemia management in acute stroke. Eur Stroke J. 2018 Mar;3 1 5 21. Open 5. Rainer Dziewas, Emilia Michou, Michaela Trapl-Grundschober et al. European Stroke Organisation and European Society for Swallowing Disorders guideline for the diagnosis and treatment of post-stroke dysphagia. Eur Stroke J. 2021 Sep;6 3 LXXXIX CXV. Open 6. Furie KL, Kasner SE, Adams RJ et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Jan;42 1 227 76. Open 7. Marios Psychogios, Alex Brehm, Elena L pez-Cancio et al. European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease. Eur Stroke J. 2022 Sep;7 3 III IV. Open 8. Powers WJ, Rabinstein AA, Ackerson T et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49 3):e46-e110. Open https://web.pathway.md/diseases/recwd1RIpW03JSM4H 27/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway 9. Bushnell C, McCullough LD, Awad IA et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 May;45 5 1545 88. Open 10. Christine Kremer, Zuzana Gdovinova, Yannick Bejot et al. European Stroke Organisation guidelines on stroke in women: Management of menopause, pregnancy and postpartum. Eur Stroke J. 2022 Jun;7 2 I XIX. Open 11. A Kobayashi, A Czlonkowska, G A Ford et al. European Academy of Neurology and European Stroke Organization consensus statement and practical guidance for pre-hospital management of stroke. Eur J Neurol. 2018 Mar;25 3 425 433. Open 12. Sonia Alamowitch, Guillaume Turc, Lina Palaiodimou et al. European Stroke Organisation ESO expedited recommendation on tenecteplase for acute ischaemic stroke. Eur Stroke J. 2023 Mar;8 1 8 54. Open 13. Stephanie Debette, Mikael Mazighi, Philippe Bijlenga et al. ESO guideline for the management of extracranial and intracranial artery dissection. Eur Stroke J. 2021 Sep;6 3 XXXIX LXXXVIII. Open 14. Martin Dennis, Valeria Caso, L Jaap Kappelle et al. European Stroke Organisation ESO guidelines for prophylaxis for venous thromboembolism in immobile patients with acute ischaemic stroke. Eur Stroke J. 2016 Mar;1 1 6 19. Open 15. Brown MD, Burton JH, Nazarian DJ et al. Clinical Policy: Use of Intravenous Tissue Plasminogen Activator for the Management of Acute Ischemic Stroke in the Emergency Department. Ann Emerg Med. 2015 Sep;66 3 322 333.e31. Open 16. James Sall, Blessen C Eapen, Johanna Elizabeth Tran et al. The Management of Stroke Rehabilitation: A Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline. Ann Intern Med. 2019 Dec 17;171 12 916 924. Open 17. Martin Holtkamp, Ettore Beghi, Felix Benninger et al. European Stroke Organisation guidelines for the management of post-stroke seizures and epilepsy. Eur Stroke J. 2017 Jun;2 2 103 115. Open 18. Persani L, Brabant G, Dattani M et al. 2018 European Thyroid Association ETA Guidelines on the Diagnosis and Management of Central Hypothyroidism. Eur Thyroid J. 2018 Oct;7 5 225 237. Open 19. US Preventive Services Task Force, Carol M Mangione, Michael J Barry et al. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2022 Aug 23;328 8 746 753. Open 20. Steven E. Kahn, Cheryl A.M. Anderson, John B. Buse et al. Standards of Care in Diabetes 2023. Diabetes Care. 2023 Jan;46 Supplement_1 S1 S291. Open 21. Chandril Chugh. Acute Ischemic Stroke: Management Approach. 2019 Jun;23 Suppl 2 S140 S146.2019 Jun;23 Suppl 2 S140 S146. Open 22. Tapuwa D Musuka, Stephen B Wilton, Mouhieddin Traboulsi et al. Diagnosis and management of acute ischemic stroke: speed is critical. 2015 Sep 8;187 12 887 93.2015 Sep 8;187 12 887 93. Open 23. Angela M Carter, Andrew J Catto, Michael W Mansfield et al. Predictive variables for mortality after acute ischemic stroke. 2007 Jun;38 6 1873 80.2007 Jun;38 6 1873 80. Open 24. Eric J ttler, Andreas Unterberg, Johannes Woitzik et al. Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke. N Engl J Med. 2014 Mar 20;370 12 1091 100. Open https://web.pathway.md/diseases/recwd1RIpW03JSM4H 28/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway 25. Gronseth GS, Mess SR. Practice advisory: Etanercept for poststroke disability: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016 Jun 7;86 23 2208 11. Open 26. Sacks D, Black CM, Cognard C et al. Multisociety consensus quality improvement guidelines for intraarterial catheter-directed treatment of acute ischemic stroke, from the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, European Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology. J Vasc Interv Radiol. 2013 Feb;24 2 151 63. Open 27. Schellinger PD, Bryan RN, Caplan LR et al. Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010 Jul 13;75 2 177 85. Open 28. Jauch EC, Saver JL, Adams HP Jr et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013 Mar;44 3 870 947. Open 29. Culebras A, Mess SR, Chaturvedi S et al. Summary of evidence-based guideline update: prevention of stroke in nonvalvular atrial fibrillation: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Feb 25;82 8 716 24. Open 30. American Association of Neurological Surgeons. Choosing Wisely AANS recommendations. Choosing Wisely. 2014. Open 31. Turc G, Bhogal P, Fischer U et al. European Stroke Organisation ESO European Society for Minimally Invasive Neurological Therapy ESMINT Guidelines on Mechanical Thrombectomy in Acute Ischemic Stroke. J Neurointerv Surg. 2019 Feb 26. pii: neurintsurg-2018 014569. Open 32. Pengfei Yang, Yongwei Zhang, Lei Zhang et al. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020 May 21;382 21 1981 1993. Open 33. Bruce C V Campbell, Peter J Mitchell, Leonid Churilov et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378 17 1573 1582. Open 34. Gregory W Albers, Michael P Marks, Stephanie Kemp et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Feb 22;378 8 708 718. Open 35. Craig S Anderson, Thompson Robinson, Richard I Lindley et al. Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke. N Engl J Med. 2016 Jun 16;374 24 2313 23. Open 36. Arthur Wang, Noorie Pednekar, Rachel Lehrer et al. DRAGON score predicts functional outcomes in acute ischemic stroke patients receiving both intravenous tissue plasminogen activator and endovascular therapy. Surg Neurol Int. 2017 Jul 18;8 149. Open 37. Jennifer E. Fugate, DO and Alejandro A. Rabinstein, MD. Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke. Neurohospitalist. 2015 Jul; 5 3 110 121. Open 38. Arturo Ren , M nica Mill n, Luis San Rom n et al. Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial. JAMA. 2022 Mar 1;327 9 826 835. Open https://web.pathway.md/diseases/recwd1RIpW03JSM4H 29/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway 39. Shinichi Yoshimura, Nobuyuki Sakai, Hiroshi Yamagami et al. Endovascular Therapy for Acute Stroke with a Large Ischemic Region. N Engl J Med. 2022 Apr 7;386 14 1303 1313. Open 40. Bruce C V Campbell, Peter J Mitchell, Timothy J Kleinig et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372 11 1009 18. Open 41. RESCUE BT Trial Investigators, Zhongming Qiu, Fengli Li et al. Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial. JAMA. 2022 Aug 9;328 6 543 553. Open 42. P Lyden, T Brott, B Tilley et al. Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group. Stroke. 1994 Nov;25 11 2220 6. Open 43. Pengfei Yang, Lili Song, Yongwei Zhang et al. Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke ENCHANTED2/MT a multicentre, open-label, blinded- endpoint, randomised controlled trial. Lancet. 2022 Nov 5;400 10363 1585 1596. Open 44. Hui-Sheng Chen, Yu Cui, Zhong-He Zhou et al. Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial. JAMA. 2023 Feb 9;e230550. Open 45. Mikael Mazighi, Sebastien Richard, Bertrand Lapergue et al. Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke BP TARGET a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2021 Apr;20 4 265 274. Open 46. N Attal, G Cruccu, R Baron et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010 Sep;17 9 1113-e88. Open 47. Xiaochuan Huo, Gaoting Ma, Xu Tong et al. Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct. N Engl J Med. 2023 Apr 6;388 14 1272 1283. Open 48. Russell Chabanne, Thomas Geeraerts, Marc Begard et al. Outcomes After Endovascular Therapy With Procedural Sedation vs General Anesthesia in Patients With Acute Ischemic Stroke: The AMETIS Randomized Clinical Trial. JAMA Neurol. 2023 Apr 3;e230413. Open 49. Silke Walter, Heinrich J Audebert, Aristeidis H Katsanos et al. European Stroke Organisation ESO guidelines on mobile stroke units for prehospital stroke management. Eur Stroke J. 2022 Mar;7 1 XXVII LIX. Open 50. Guillaume Turc, Georgios Tsivgoulis, Heinrich J Audebert et al. European Stroke Organisation European Society for Minimally Invasive Neurological Therapy expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischaemic stroke and anterior circulation large vessel occlusion. Eur Stroke J. 2022 Mar;7 1 I XXVI. Open 51. Catharina Jm Klijn, Maurizio Paciaroni, Eivind Berge et al. Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation: A European Stroke Organisation guideline. Eur Stroke J. 2019 Sep;4 3 198 223. Open 52. Jesse Dawson, ine Merwick, Alastair Webb et al. European Stroke Organisation expedited recommendation for the use of short-term dual antiplatelet therapy early after minor stroke and high-risk TIA. Eur Stroke J. 2021 Jun;6 2 CLXXXVII CXCI. Open 53. Else Charlotte Sandset, Craig S Anderson, Philip M Bath et al. European Stroke Organisation ESO guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage. Eur https://web.pathway.md/diseases/recwd1RIpW03JSM4H 30/31 6/23/23, 1:57 AM Acute ischemic stroke Pathway Stroke J. 2021 Jun;6 2 XLVIII LXXXIX. Open 54. Eivind Berge, William Whiteley, Heinrich Audebert et al. European Stroke Organisation ESO guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021 Mar;6 1 I LXII. Open 55. Nadinda A M van der Ende, Bob Roozenbeek, Lucas E M Smagge et al. Safety and Efficacy of Dual Thrombolytic Therapy With Mutant Prourokinase and Small Bolus Alteplase for Ischemic Stroke. JAMA Neurol. 2023 May 22;e231262. Online ahead of print. Open 56. Steven J Warach, Anna Ranta, Joosup Kim et al. Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke CERTAIN Collaboration. JAMA Neurol. 2023 May 30;e231449. Open https://web.pathway.md/diseases/recwd1RIpW03JSM4H 31/31