neurologic disorders
Ischemic Stroke
Treatment of Ischemic Stroke
General stroke treatments Acute antihypertensive therapy only in certain circumstances For acute treatment, sometimes reperfusion with recombinant tissueplasminogenactivator ortenecteplaseand/or mechanical thrombectomy Sometimes carotid endarterectomy or stenting Antiplatelet therapy Sometimes anticoagulation Long-term control of risk factors For long-term treatment, rehabilitation Guidelines for early management of stroke are available from theAmerican Heart Association and American Stroke Association. Patients with acute ischemic strokes are usually hospitalized. Treatment such as the following may be needed during initial evaluation and stabilization. Airway support and ventilatory assistance if decreased consciousness or bulbar dysfunction compromises the airway Supplemental oxygen only if needed to maintain oxygen saturation > 94% Correction of hyperthermia (temperature > 38° C) by using an antipyretic medication and identifying and treating the cause of hypothermia Treatment of hypoglycemia (blood glucose < 60 mg/dL) Treatment of hyperglycemia to lower blood glucose to 140 to 180 mg/dL while closely monitoring for hypoglycemia Perfusion of an ischemic brain area may require a high blood pressure (BP) because autoregulation is lost; thus, BP should not be decreased except in the following cases: There are signs of other end-organ damage (eg, Aortic Dissection , Use of recombinant tissueplasminogenactivator (tPA) and/or mechanical thrombectomy is likely. If BP is ≥ 220 mm Hg systolic or ≥ 120 mm Hg diastolic on 2 successive readings 15 minutes apart, lowering BP by 15% in the 24 hours after stroke onset is reasonable. For patients who are eligible for acute reperfusion therapy, BP is treated to decrease it to < 180/105 mm Hg before starting IV thrombolysis with one of the following: Labetalol10 to 20 mg IV bolus over 1 to 2 minutes (may repeat 1 time) Nicardipine5 mg/hour IV infusion initially (dose is increased by 2.5 mg/hour every 5 to 15 minutes to a maximum of 15 mg/hour) Clevidipine1 to 2 mg/hour IV infusion (titrate by doubling the dose every 2 to 5 minutes until desired BP is reached to a maximum of 21 mg/hour) Patients with presumed thrombi or emboli may be treated with one or a combination of the following: tPA, thrombolysis-in-situ, and/or mechanical thrombectomy Antiplatelet medications Anticoagulants Most patients are not candidates for thrombolytic therapy; they should be given an antiplatelet medication (usuallyaspirin325 mg orally) when they are admitted to the hospital. Contraindications to antiplatelet medications includeaspirin-induced or nonsteroidal anti-inflammatory drug (NSAID)-induced asthma or urticaria, other hypersensitivity toaspirinor to tartrazine, acute gastrointestinal bleeding, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and use ofwarfarin. Recombinant tPA(alteplase) can be used for patients with acute ischemic stroke up to 3 hours after symptom onset if they have no contraindications to tPA (see table). Some experts recommend using tPA up to 4.5 hours after symptom onset (seeExpansion of the Time Window for Treatment of Acute Ischemic Stroke With Intravenous Tissue Plasminogen Activator); however, between 3 hours and 4.5 hours after symptom onset, additional exclusion criteria apply (see table). Thus, tPA must be given within 4.5 hours of symptom onset—a difficult requirement. Because the precise time of symptom onset may not be known, clinicians must start timing from the moment the patient was last observed to be well. Although tPA can cause fatal or other symptomatic brain hemorrhage, patients treated with tPA strictly according to protocols still have a higher likelihood of functional neurologic recovery. Only clinicians experienced in stroke management should use tPA to treat patients with acute stroke; inexperienced physicians are more likely to violate protocols, resulting in more brain hemorrhages and deaths. When tPA is given incorrectly (eg, when given despite the presence of exclusion criteria), risk of hemorrhage due to tPA is high mainly for patients who have had stroke; risk of brain hemorrhage is very low (about 0.5%; 95% confidence interval of 0 to 2.0% [ Treatment references ]) for patients who have had a stroke mimic (eg, hemiplegic migraine, certain CNS infections, postictal paralysis, functional neurologic disorders). If experienced clinicians are not available on site, consultation with an expert at a stroke center (including video evaluation of the patient [telemedicine]), if possible, may enable these clinicians to use tPA. Because most poor outcomes result from failure to strictly adhere to the protocol, a checklist of inclusion and exclusion criteria should be used. Before treatment with tPA, the following are required: Brain hemorrhage must be excluded by CT Systolic BP must be < 185 mm Hg Diastolic BP must be < 105 mm Hg Blood glucose must be > 50 mg/dL Antihypertensives (IVnicardipine, IVlabetalol, IVclevidipine) may be given as above. BP should be kept < 180/105 mm Hg for at least 24 hours after treatment with tPA. Dose of tPA is 0.9 mg/kg IV (maximum dose 90 mg); 10% is given by rapid IV injection over 1 minute, and the remainder by constant infusion over 60 minutes. Vital signs are closely monitored for 24 hours after treatment. Any bleeding complications are aggressively managed. Anticoagulants and antiplatelet medications are not used within 24 hours of treatment with tPA. ( Acute stroke treatment ). in the therapeutic window after onset of stroke symptoms ( Treatment references ). Nevertheless, if patients have any of the following conditions, the risk of bleeding with Recent major surgery or procedure (eg, coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels) Cerebrovascular disease Recent intracranial hemorrhage Recent gastrointestinal or genitourinary bleeding Recent trauma Hypertension (systolic BP > 175 mm Hg or diastolic BP > 110 mm Hg Acute pericarditis Subacute bacterial endocarditis Hemostatic defects including those due to severe hepatic or renal disease Significant hepatic dysfunction Pregnancy Hemorrhagic diabetic retinopathy or other hemorrhagic ophthalmic conditions Septic thrombophlebitis or occluded arteriovenous cannula at an infected site Advanced age (> 77 years) Current use of anticoagulants (eg,warfarin) Thrombolysis-in-situ(angiographically directed intra-arterial thrombolysis) of a thrombus or embolus is almost obsolete except when a clot is too distal to be accessed by catheters (eg, distal A2 [anterior cerebral artery distal to the anterior communicating artery]). Mechanical thrombectomy(angiographically directed intra-arterial removal of a thrombus or embolus by a stent retriever device) is standard of care in large stroke centers for patients with recent large-vessel occlusion in the anterior circulation. Mechanical thrombectomy had previously been restricted to use within 6 hours of symptom onset in patients with internal carotid artery or middle cerebral artery occlusion. However, at comprehensive stroke centers, clinical and/or imaging findings that suggest a substantial amount of tissue at risk of infarction (penumbra) may justify later treatment. For example, the volume of infarcted tissue and at-risk underperfused tissue (ischemic penumbra) can be identified using perfusion CT or perfusion MRI. A sizeable mismatch between the infarct and at-risk volume identified by diffusion-weighted or perfusion-weighted imaging suggests that substantial penumbra is still potentially salvageable. In the DEFUSE 3 trial, benefit was evident up to 16 hours after symptom onset in patients with a small infarct and a larger penumbra; both findings are based on imaging criteria ( Treatment references ). In the DAWN trial, benefit was evident up to 24 hours after symptom onset in patients with a large mismatch between infarct volume based on imaging and severity of the clinical deficit based on clinical criteria ( Recently, evidence for the efficacy of mechanical thrombectomy in patients with posterior circulation strokes has been growing ( Treatment references ). In the past, clinical trials restricted mechanical thrombectomy to patients with an NIHSS score > 6; however, recent evidence supports the usefulness of mechanical thrombectomy in patients with an NIHSS < 6 ( Treatment references ). Current evidence supports the use of mechanical thrombectomy with IV thrombolysis (bridging therapy) for all patients who are otherwise eligible for thrombolysis ( Treatment references ). It should not be used as an alternative to IV recombinant tPA for patients with acute ischemic stroke if they are eligible for tPA. Devices used to remove thrombi are being improved, and recent models reestablish perfusion in 90 to 100% of patients. Oral antiplatelet medicationsare used in acute stroke treatment to reduce the risk of recurrent disabling stroke. The following may be used: Aspirin81 to 325 mg within 48 hours of stroke onset Dual antiplatelet therapy withaspirinplusclopidogrel:Aspirinplusclopidogrel(eg, 300 to 600 mg orally once, then 75 mg orally once a day) within 24 hours of stroke onset for patients with minor stroke or at high risk of a transient ischemic attack (TIA; ABCD2 score ≥ 4) Dual antiplatelet therapy withaspirin81 mg andticagrelorwith a loading dose of 180 mg on day 1 followed by 90 mg twice a day (possibly beneficial for patients withclopidogrelresistance CYP2C19 loss of function allele, especially if an extracranial or intracranial stent is used) given within 48 hours reduces the risk of early recurrent stroke and death ( Treatment references ). alone for reducing risk of stroke in the first 90 days and does not increase risk of hemorrhage ( Treatment references ). However, prolonged (eg, > 3 months) use of Anticoagulationwithheparinor low molecular weightheparinis used for stroke caused by cerebral venous thrombosis and sometimes for stroke caused by cervical artery dissection. Anticoagulation can also be used in patients at high risk of recurrent cardiac emboli (eg, those with cardiac thrombi or mechanical valves). Usually, anticoagulation is avoided in the acute stage because risk of hemorrhage (hemorrhagic transformation) is higher, especially with large infarcts. Supportive careis continued during convalescence: Controlling hyperglycemia and fever can limit brain damage after stroke, leading to better functional outcomes. Screening for dysphagia before patients begin eating, drinking, or receiving oral medications can help identify patients at increased risk of aspiration; it should be done by a speech-language pathologist or other trained health care practitioner. Enteral nutrition if needed should be started within 7 days of admission after an acute stoke. Intermittent pneumatic compression (IPC) for Prevention is recommended for immobile stroke patients without contraindications. Low molecular weightheparinmay be given to immobile stroke patients without contraindications. Measures to prevent Prevention are started early. Physical therapy to help maximize function and prevent sarcopenia and joint contractures Long-term management also focuses on prevention of recurrent stroke (secondary prevention). Modifiable risk factors (eg, Hypertension , Diagnosis often occurs after a stroke and may interfere with recovery. Treatment of depression may aid in recovery, Clinicians should ask patients whether they are feeling sad or have lost interest or pleasure in doing formerly enjoyable activities. Clinicians should also ask family members whether they have noticed any signs of depression in the patient. Extracranial carotid endarterectomy or stentingis indicated for patients with recent nondisabling, submaximal stroke attributed to an ipsilateral carotid obstruction of 70 to 99% of the arterial lumen or to an ulcerated plaque if life expectancy is at least 5 years. In other symptomatic patients (eg, patients with TIAs), endarterectomy or stenting with antiplatelet therapy is indicated for carotid obstruction of≥60% with or without ulceration if life expectancy is at least 5 years. These procedures should be done by surgeons and interventionists who have a successful record with the procedure (ie, morbidity and mortality rate of<3%) in the hospital where it will be done. If carotid stenosis is asymptomatic, endarterectomy or stenting is beneficial only when done by very experienced surgeons or interventionists, and that benefit is likely to be small. For many patients, carotid stenting with an emboli-protection device (a type of filter) is preferred to endarterectomy, particularly if patients are ≥ 70 years and have a high surgical risk. Carotid endarterectomy and stenting are equally effective for stroke prevention. In the periprocedural period, myocardial infarction is more likely after endarterectomy, and recurrent stroke is more likely after stenting. Extracranial vertebral angioplasty and/or stentingcan be used in certain patients with recurrent symptoms of vertebrobasilar ischemia despite optimal medical treatment and a vertebral artery obstruction of 50 to 99%. may be effective in patients when optimal treatment with medications has been ineffective. Key factors to consider are patient characteristics (eg, control of risk factors, adherence to the medication regimen), timing of the procedure (> 3 weeks after the stroke), and the interventionist's experience. Recent evidence indicates that the rate of periprocedural adverse events can be acceptably low after percutaneous transluminal angioplasty and stenting when these factors are considered ( Treatment references ). plus use of antiplatelet therapy is recommended for patients < 60 years with an embolic stroke of undetermined cause despite extensive evaluation ( Treatment references , Oral antiplatelet medicationsare used to prevent subsequent noncardioembolic (atherothrombotic, lacunar, cryptogenic) strokes (secondary prevention). The following may be used: Aspirin81 or 325 mg once a day Clopidogrel75 mg once a day Ticagrelor90 mg twice a day The combination productaspirin25 mg/extended-releasedipyridamole200 mg 2 times a day In patients takingwarfarin, antiplatelet medications additively increase risk of bleeding and are thus usually avoided; however,aspirinis occasionally used simultaneously withwarfarinin certain high-risk patients.Clopidogrelis indicated for patients who are allergic toaspirin. If ischemic stroke recurs or if a coronary artery stent becomes blocked while patients are takingclopidogrel, clinicians should suspect impaired metabolism ofclopidogrel(ineffective conversion ofclopidogrelto its active form because cytochrome P-450 2C19 [CYP2C19] activity is reduced); a test to determine CYP2C19 status (eg, genetic testing for CYP450 polymorphisms) is recommended. If impaired metabolism is confirmed,aspirinor combinationaspirinandticagreloris a reasonable alternative. Clopidogrelplusaspirin, if started during acute treatment, is given for only a short time (eg, < 3 weeks) because it has no advantage overaspirinalone in long-term secondary stroke prevention and results in more bleeding complications.Clopidogrelplusaspirinbefore and for ≥ 30 days after stenting is indicated, usually for ≤ 6 months; if patients cannot tolerateclopidogrelor haveclopidogrelresistance due to CYP2C19 loss of allele,ticagrelor90 mg twice a day can be substituted. Oral anticoagulantsare indicated for secondary prevention of cardioembolic strokes (as well as primary prevention). Adjusted-dosewarfarin(a vitamin K antagonist) with a target international normalized ratio (INR) of 2 to 3 is used for certain patients with nonvalvular or valvular atrial fibrillation. A target INR of 2.5 to 3.5 is used if patients have a mechanical prosthetic cardiac valve. Efficacious alternatives towarfarinfor patients with nonvalvular atrial fibrillation include the following new anticoagulants: Dabigatran(a directthrombininhibitor) 150 mg twice a day in patients without severe renal failure (creatinine clearance < 15 mL/minute) and/or liver failure (elevated INR) Apixaban(a directfactor Xainhibitor) 5 mg twice a day; 2.5 mg if patients have ≥ 2 of the following: age > 80 years, weight < 60 kg, serum creatinine ≥ 1.5mg/dL Rivaroxaban(a directfactor Xainhibitor) 20 mg once a day for patients without severe renal failure (creatinine clearance < 15 mL/minute) ( Treatment references ), and the antidote for Statinsare used to prevent recurrent strokes; lipid levels must be decreased by substantial amounts.Atorvastatin80 mg orrosuvastatin40 mg once a day is recommended for patients with evidence of atherosclerotic stroke and LDL (low-density lipoprotein) cholesterol ≥ 100 mg/dL. 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