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ischemic stroke

A stroke caused by an insufficient supply of blood & oxygen to a part of the brain, generally result of cerebrovascular disease. Etiology: 1) thrombus related to atherosclerosis of large arteries (30%) a) internal carotids b) aortic arch {uncommon} [24] c) large intracranial arteries d) cervicocephalic arterial dissection 2) embolus from cardiac source (20%) a) secondary hemorrhage may occur b) patent foramen ovale [24,31], - cryptogenic stroke, all ages, epecially < 55-60 c) atrial septal aneurysm in 28-40% of ischemic strokes in patients < 55 years of age d) patent foramen ovale & atrial septal aneurysm frequently occur together e) multiple cardiac emboli are suggested by 2 or more areas of ischemic infarction f) myocardial infarction [11] resulting in LV systolic dysfunction g) atrial fibrillation [11] - 25% of patients with cryptogenic embolic stroke have paroxysmal atrial fibrillation [3,60,77]; 12-16% [66] - cardiac surgery increases risk of atrial fibrillation [3] 3) lacunar (small vessel) (20%) a) lipohyalinosis b) atherosclerosis c) vasculitis 4) other (30%) a) pharmacologic: 1] oral contraceptives a] controversial b] avoid in women with migraine or who smoke 2] cocaine 3] over the counter sympathomimetics b) hypercoagulable state 1] antiphospholipid antibody, especially high titer IgG anticardiolipin 2] protein S deficiency 3] protein C deficiency 4] antithrombin III deficiency 5] polycythemia vera 6] disseminated intravascular coagulaton (DIC) 7] thrombotic thrombocytopenic purpura 8] hyperhomocysteinemia c) arteritis 1] giant cell arteritis 2] Takayasu arteritis d) cervical artery dissection due to trauma e) fibromuscular dysplasia f) migraine g) Moya Moya disease h) children's medical visits for respiratory tract infection (within 3 days) confer 12-fold increase in risk for ischemic stroke [68]* 5) idiopathic in 50% of patients < 55 years of age [41] - embolic stroke of undetermined source [3] - suspect embolus from cardiac source (see above) - paroxysmal atrial fibrillation in 25% of patients with idiopathic stroke [54,77] 6) also see risk factors for ischemic stroke * Editorialist not impressed. Absolute risk is very low, No evidence that attempt to treat would mitigate risk. [58] Epidemiology: 1) 3rd most common cause of death 2) most common cause of adult disability 3) most preventable of catastrophic conditions 4) 75% of all strokes are ischemic 5) persons with type A blood have 16% higher risk for early-onset stroke than persons with other blood types [118] - persons with type O blood have 12% lower risk [118] 6) states with high stroke mortality [93] - Alabama, Alaska, Arkansas, Louisiana, Mississippi, Oklahoma, Tennessee, South Carolina, or West Virginia Pathology: 1) infarction of a vascular territory of the brain due to ischemia 2) an ischemic zone surrounds an infarct & secondary phenomena increase the severity of the irreversible injury 3) these secondary phenomena include excitotoxin-induced neuronal injury, cerebral edema & altered local blood flow 4) morbidity & mortality associated with massive hemispheric ischemic strokes is due to brain tissue edema resulting in brainstem & diencephalic compression [23] Genetics: - susceptibility to ischemic stroke associated with a) defects in protein kinase C-eta (PRKCH) b) defects in P-selectin (SELP) c) genetic variations in ALOX5AP d) defects in factor V e) defects in prothrombin f) polymorphisms in IL4 g) defects in CECR1 (lacunar infarcts) Clinical manifestations: 1) focal or multifocal neurologic deficit evolving over second to minutes, persisting > 24 hours 2) sensory involvement of affected areas may result in sensory deficits 3) motor involvement of affected areas may result a) paresis, paralysis, generally unilateral b) dysarthria, dysphagia 4) transient improvement in renal function may occur in patients with renal insufficiency (central regulation hypothesized) [85] 5) suspect vertebrobasilar stroke in older patients with acute onset vertigo [3] Laboratory: - telomere length in peripheral blood mononuclear cells allegedly predicts cognitive decline, dementia & death after stroke [27] - difficult to envision mechanism Special laboratory: - prestroke trailmaking B test may predict risk of first stroke & mortality after first stroke - cardiac rhythm monitoring (in hospital telemetry) for atrial fibrillation - at least 24 hours of Holter monitoring [88] - prolonged outpatient cardiac rhythm monitoring indicated for patients with embolic stroke [3] - 30-day event-triggered recorder more sensitive than 24 hour HOLTER* - 6 months of monitoring with an insertable cardiac monitor [6] - 10 day HOLTER monitoring 3 times within 6 months [90] - atrial fibrillation identified in 25% if patients with idiopathic stroke - swallowing evaluation for dysphagia after stroke [3] * it is not clear how or why the events were triggered Radiology: 1) head CT to rule out intracranial hemorrhage [3] 2) magnetic resonance imaging (MRI) a) may be useful to identify patients who might benefit from endovascular thrombolysis up to 12 hours after an ischemic stroke [49] b) CT or MRI within 8 hours after onset of stroke symptoms to predict which patients might benefit from endovascular thrombolysis does not improve outcomes [53] c) diffusion-weighted imaging may be more sensitive 3) magnetic resonance angiography or CT angiography useful for evaluating extracranial & large intracranial arteries [3] - indicated for arterial thrombectomy 4) angiography is the gold standard for delineating vascular anatomy, but rarely used (associated with small risk of stroke) [3] 5) identify collateral circulation to determine likely benefit of thrombectomy (see Management) 6) carotid ultrasound 7) transcranial doppler ultrasound showing increased flow velocity can confirm magnetic resonance angiographic findings 8) transthoracic echocardiogram - identifies atrial septal defect in young adults with stroke - transesophageal ultrasound not routinely indicated - can also detect aortic arch thrombi: thrombi > 3 mm are suspect Complications: 1) cerebral edema or cerebellar edema resulting in increased intracranial pressure may occur after major ischemic stroke - middle cerebral artery (MCA) territory infarcts with life-threatening edema (malgnant MCA infarcts) associated with 80% mortality [64] 2) conversion to hemorrhagic stroke, usually within 48 hours 3) delirium occurs in 12% of patients admitted to stroke unit; associated with poor prognosis [40] 4) seizures early after stroke a) less common with ischemic stroke than hemorrhagic stroke (4% vs 15%) [43] b) more common with cortical stroke than subcortical stroke (19% vs 10%) c) do not predict mortality or function at 6 months [43] 5) risk of pneumonia is highest in the 1st week after stroke [120] 6) poststroke dementia due to cerebrovascular disease [45] 7) anxiety & depression common [3,46] - major depression with psychosis is a further complication 8) fatigue after stroke due to depression, sleep apnea, heart failure [3] 9) recurrence of stroke - risk highest with atherosclerotic stenosis of large artery of >70% [3] - risk of recurrent stroke lower with atrial fibrillation diagnosed after stroke than before [98] 10) death, recurrent stroke, MI, or admission to a care facility more common in stroke (without 90 day complications) than in controls 10% vs 5% at 1 year, 24% vs 14% at 3 years & 36% vs 21% at 5 years [92] - particulate matter pollution, especially smaller particulate matter is a risk factor for in-hospital stroke-associated mortality [113] 11) reemergence or recrudescence of stroke symptoms in the setting of an intercurrent illness [103] 12) atrial fibrillation diagnosed after stroke (10%) [98] - neurogenic mechanism suggested [98] Differential diagnosis: - see stroke Management: 1) acute ischemic stroke (within 4 hours, 4.5 hours [37]) a) see ACLS algorithm for suspected stroke b) see thrombolysis for ischemic stroke - helpful when administered within 3-4.5 hours of stroke symptom [105] - thrombolysis within 90 minutes provides best outcomes [57] - mobile stroke units may reduce time to thrombolysis c) NCY-059, a free radical trapping agent, 72 hour infusion appears to improve outcomes in clinical trials [21] d) endovascular thrombectomy - within 24 hours if suspected large vessel occlusion [3,96] - within 6-16 hours of anterior-circulation large-vessel occlusion [105] - following tPA - tenecteplase may be reasonable alternative to alteplase if eligible for arterial thrombectomy [105] - CT angiography determines large vessel occlusion & elgiblity for arterial thrombectomy - endovascular thrombectomy with retrievable stent - intracranial stenting associated with 2-fold increase in risk or stroke vs medical therapy [3] - may be beneficial in patients with acute ischemic stroke due to proximal intracranial arterial occlusion [36,51,72,73,78,81] - patients < 80 years - thrombus in the internal carotid artery or proximal middle cerebral artery - thrombectomy without stent ??; do not stent symptomatic patient [3] - few comorbidities & no contraindications [82] - 45% functional independence at 90 days vs 32% for tPA alone [82] - benefit only if begun within 7 hours of symptom onset [89] - patients with poor collateral circulation generally progress to rapid tissue infarction, & interventional treatment may be futile [94] e) hemicraniectomy may reduce intracranial pressure from malignant middle cerebral artery (MCA) infarcts involving > 50% of arterial territory [3,23,64] f) antiplatelet therapy for patients who arrive outside the window for thrombolysis for ischemic stroke [3] - see pharmacologic therapy post stroke below 2) general guidelines (see stroke) 3) blood pressure control [62,71] a) do not attempt to acutely lower blood pressure unless 1] systolic blood pressure > 220 mm Hg, or 2] diastolic blood pressure > 120 mm Hg, or 3] mean arterial blood pressure > 140 mm Hg 4] patient has acute coronary syndrome 5] aortic dissection suspected 6] thrombolytic therapy planned [4] b) systolic BP > 230 mm Hg or diastolic BP 121-140 mm Hg 1] labetolol 10 mg IV, over 1-2 min q 10 min up to 150 mg 2] nicardipine IV is an alternative 3] if response in inadequate, use sodium nitroprusside c) diastolic BP > 140 mm Hg 1] nitroprusside 0.5-10 ug/kg/min 2] monitor closely - nitroprusside effective for malignant hypertension, but may increase intracranial pressure [8] d) avoid hypotension [3,58] e) see risk factors for & prevention of ischemic stroke for long-term post ischemic stroke blood pressure control 4) glycemic control - tight glycemic control (< 130 mg/dL) no better than standard control (< 180 mg/dL) during 1st 72 hours after stroke [102] - MKSAP 16 recommends maintaining blood glucose < 140 mg/dL at least for 1st 24 hours [3] - tight glycemic control (blood glucose 72-135 mg/dL) of no benefit immediately after ischemic stroke [74] - number needed to harm = 7 hypoglycemia [74] 5) supportive therapy directed towards: a) reducing risk factors (attenuating pathologic processes) b) removing underlying cause c) minimizing secondary brain damage by maintaining adequate perfusion & limiting edema d) monitor for cerebral edema for 3-5 days post stroke [3] e) avoid postural hypotension, a frequent cause of neurologic deterioration after completion of ischemic stroke 1] return to supine position - supine vs sitting up has no effect on disability or mortality after acute stroke [91] 2] administer fluids to maintain euvolemia (normal saline) 3] monitor blood pressure 4] reassess pharmacologic therapy f) avoid/treat hyperthermia or fever with acetaminophen - routine acetaminophen of no benefit [38] 6) inpatient telemetry to evaluate for atrial fibrillation [3] 7) pharmacologic therapy post stroke a) thrombolytic therapy (within 1st 4.5 hours) - tissue plasminogen activator (tPA, Alteplase) - disability-free survival at 90 days 35% with tPA vs 30% with endovascular approach [51] - endovascular therapy after tPA of no benefit [52] b) heparin* followed by warfarin - do NOT use - for embolic stroke, use asprin for 4-14 days, then switch to anticoagulation [3] c) antiplatelet therapy 1] all patients within 24 hours, unless contraindicated [3,59,105] - avoid for 2-7 days if hemorrhagic transformation involving hematoma [3] 2] clopidogrel (Plavix) 75 mg PO QD superior to aspirin [3,32] 3] aspirin 325 mg QD - 650 mg BID for intracranial arterial stenosis - 160-300 mg QD, started within 48 hours of onset improves long-term outcome [75] - aspirin reduces risk of recurrent stroke by 93% at 2 weeks & 74% at 12 weeks relative to placebo [86] - aspirin + dipyridamole superior to aspirin alone in preventing recurrent stroke [3] 4] dual antiplatelet therapy - American Heart Association endorses dual antiplatelet therapy for 21 days [3,124] - dual antiplatelet therapy increases risk of systemic bleeding ~5-6 events per 100 patient-years relative to monotherapy [97] - dual antiplatelet therapy decreases risk of stroke at the cost of increased risk for major hemorrhage (09% vs 0.2%) [99,106] - dual antiplatelet therapy may not increase risk of intracerebral hemorrhage [97]; it does [106] - short-term (up to 3 weeks) dual antiplatelet therapy with aspirin plus clopidogrel or ticagrelor for minor ischemic stroke,then aspirin alone [101,106,124] - 30 day outcomes for dual antiplatelet therapy with ticagrelor + aspirin 75-100 mg for moderate ischemic stroke better than aspirin alone [110] - dual antiplatelet therapy should not be used in patients with major stroke due to increased risk for intracranial bleeding [101] - long-term dual antiplatelet therapy does not decrease risk of stroke but increases risk of hemorrhage & death vs single antiplatelet agent [3] - presence of an acute infarct on index imaging is associated with an increased risk of recurrent stroke & a more pronounced benefit from dual antiplatelet therapy [112] d) patients should receive high-intensity statin with aspirin in the acute post-stroke period [3,44] - statins have not been shown to reduce risk of recurrent stroke when administered within 30 days [3] e) minocycline 200 mg PO QD for 5 days (window 6-24 hours after onset of stroke) [29] f) SSRI to improve outcomes in patients with stroke controversial [61] - fluoxetine 20 mg PO QD for 90 days starting 5-10 days after stroke may diminish motor disability [39] - fluoxetine of no benefit at 6 months [108] g) ginkgo biloba extract (450 mg QD) + aspirin associated with less cognitive decline following stroke than aspirin alone [95] 8) blood pressure reduction predicts poor prognosis: [14] a) reduction in blood pressure (both systolic or diastolic) during the 1st 24 hours associated with negative outcomes b) antihypertensive therapy does not seem to affect either blood pressure or outcome during the 1st 24 hours [14] c) lowering systolic blood pressure by 10-20% within 24-48 hours does not affect morbidity or mortality [121] d) initial blood pressure < 150/70 mm Hg associated with increased mortality e) do not initiate antihypertensive treatment in the 1st 48 hours unless - systolic BP > 220 mm Hg, diastolic BP > 120 mm Hg (MKSAP19) [3] - acute coronary syndrome, aortic dissection, end-organ damage [3] f) if patient eligible for thrombolysis for ischemic stroke - systolic BP < 180 mm Hg, diastolic BP < 105 mm Hg with pressures maintained for 24 hours after therapy [3] g) intensive control of systolic blood pressure to <120 mm Hg after endovascular thrombectomy may compromise functional recovery [117] 9) swallowing evaluation for dysphagia prior to administraion of oral meds [3] 10) stroke units (neurorehabilitation) improve outcomes [44,83] (see neurorehabilitation) 11) telestroke systems of benefit for rural areas (see telehealth) 12) early mobilization - mobilization in 1st 24 hours of no benefit, possibly harmful [79] - if not, DVT prophylaxis within 48 hours [3] - LMW heparin, do not use warfarin, DOAC not FDA approved use [44] - graduated compression stockings of no benefit [] 13) remote ischemic conditioning may improve neurologic function [116] - of no benefit [119] 14) secondary prevention [3,4,12,15,16,26,28,32,42,44,47,55,56,65] - see prevention of ischemic stroke - target LDL cholesterol < 70 mg/dL [104] - see embolic stroke - routine evaluation for thrombophilia not indicated [3] - anticonvulsant not indicated unless patient has had a seizure [3] - carotid endarterectomy not indicated for 100% carotid artery stenosis [3] - use of chlorthalidone vs HCTZ associated with lower cardiovascular morbidity & mortality after myocardial infarction or ischemic stroke [105] 15) prognosis - most stroke survivors have neurologic impairment after 1 years - severity of initial neurologic deficit is the strongest predictor of long-term disability [3, 123] - premorbid condition, age & post-stroke complications also predict prognosis [123] - magnitude of chronic cognitive impairment after stroke cannot be determined for at least 3 months [44] - childhood & young adult ischemic stroke associated with similar prognosis, 55% considered favorable by Rankin scale scores [80] - depression is prevalent & treatment of depression is one of the long-term modifiable disability factors [3] 14) advance directives documented with a minority of patients [87] * unfractionated heparin & low-molecular-weight heparin not as effective as aspirin for acute ischemic stroke [12] * LMW heparin for DVT prophylaxis, do not use warfarin, DOAC not FDA-approved Follow-up: - neurorehabilitation (see above) - workup for coronary artery disease a) lipid panel* b) rule out hyperhomocysteinemia c) ECG stress testing - wait at least 6-9 months [3,67,114] after ischemic stroke prior to elective non-cardiac surgery - risk of perioperative stroke & death remains elevated to 2 years [115] Notes: - 'Get with the Guidelines - Stroke' an internet-based tool improved outcomes in hospitalized stroke patients [34] - frequency of gastrostomy tube placement varies substantially among U.S. hospitals [69]

Interactions

disease interactions

Related

ACLS algorithm for suspected stroke atherosclerotic intracranial arterial stenosis carotid artery disease endovascular thrombectomy for acute ischemic stroke ischemic stroke prevention trial mobile stroke unit; STroke Emergency MObile (STEMO) neurorehabilitation prevention of ischemic stroke reversible ischemic neurologic deficit (RIND) risk factors for & prevention of ischemic stroke secondary prevention in patients with cardiovascular disease thrombolysis for ischemic stroke transient ischemic attack (TIA)

Specific

anterior cerebral artery syndrome embolic stroke lacunar infarct middle cerebral artery syndrome (M1 stenosis) posterior cerebral artery syndrome vertebrobasilar stroke

General

stroke; cerebrovascular accident (CVA) cerebral ischemia

Database Correlations

OMIM 601367

References

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