malformations. They require vascular imaging tests (eg, CTA, MRA, and/or conventional angiography). SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 24/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Hemorrhagic stroke (The Basics)" and "Patient education: Stroke (The Basics)") Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Classification Cerebrovascular disease is caused by one of several pathophysiologic processes ( table 1 and table 2) involving the blood vessels of the brain. (See 'Classification' above.) Initial evaluation Sudden loss of focal brain function is the core feature of the onset of ischemic stroke. However, patients with conditions other than stroke can present in a similar fashion ( table 3). The initial evaluation requires a rapid but broad assessment to stabilize vital signs, determine if intracranial hemorrhage is present, and decide if reperfusion therapy with intravenous thrombolysis ( table 4) or mechanical thrombectomy is warranted for patients with ischemic stroke. (See 'Initial general assessment' above and 'Is the patient a candidate for reperfusion?' above.) https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 25/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Determining the type of stroke After completing the initial assessment, the goal of the subsequent evaluation is to determine the underlying pathophysiology of the stroke based upon the history, physical examination, and initial neuroimaging findings ( table 1). Certain constellations of symptoms and signs can suggest a specific ischemic process ( table 5). (See 'Determining a presumptive diagnosis of stroke subtype' above.) Confirming the diagnosis Confirming the precise pathophysiologic process is aided by more directed diagnostic testing, including cardiac studies and neurovascular imaging. (See 'Confirming the diagnosis' above.) Cardiac monitoring Cardiac monitoring for at least the first 24 hours after the onset of ischemic stroke is useful to look for arrhythmias. For patients with a cryptogenic ischemic stroke or transient ischemic attack (TIA) and no evidence of atrial fibrillation on electrocardiogram (ECG) and 24-hour cardiac monitoring, we suggest ambulatory cardiac monitoring for several weeks. All patients with suspected embolic stroke should have an echocardiogram. (See 'Cardiac evaluation' above and 'Echocardiography' above.) Blood tests A number of blood tests are indicated in patients with brain ischemia, including a complete blood count, platelet count, prothrombin time and partial thromboplastin time, and serum lipids. However, indications to test for hypercoagulable disorders are limited. Furthermore, it remains unclear if the inherited thrombophilias directly predispose to arterial stroke as they do to venous thrombosis. (See 'Blood tests' above.) Evaluation for a bleeding disorder in patients with hemorrhagic stroke In this setting, all patients require platelet count, prothrombin time, activated partial thromboplastin time, and thrombin time and/or ecarin clotting time if the patient is known or suspected to be taking a direct thrombin inhibitor or a direct factor Xa inhibitor. (See 'Evaluation of patients with intracerebral hemorrhage' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Caplan LR. Terms describing brain ischemia by tempo are no longer useful: a polemic (with apologies to Shakespeare). Surg Neurol 1993; 40:91. 2. Caplan LR. TIAs: we need to return to the question, 'What is wrong with Mr. Jones?'. Neurology 1988; 38:791. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 26/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate 3. Gorelick PB, Hier DB, Caplan LR, Langenberg P. Headache in acute cerebrovascular disease. Neurology 1986; 36:1445. 4. Ginsberg MD, Busto R. Combating hyperthermia in acute stroke: a significant clinical concern. Stroke 1998; 29:529. 5. Caplan LR. Imaging and laboratory diagnosis. In: Caplan's Stroke: A Clinical Approach, 4th, S aunders, Philadelphia 2009. p.87. 6. Moncayo J, Devuyst G, Van Melle G, Bogousslavsky J. Coexisting causes of ischemic stroke. Arch Neurol 2000; 57:1139. 7. Barnett HJ, Gunton RW, Eliasziw M, et al. Causes and severity of ischemic stroke in patients with internal carotid artery stenosis. JAMA 2000; 283:1429. 8. Caplan LR. Diagnosis and the clinical encounter. In: Caplan's Stroke: A Clinical Approach, 4th, Saunders, Philadelphia 2009. p.64. 9. Caplan LR, Gorelick PB, Hier DB. Race, sex and occlusive cerebrovascular disease: a review. Stroke 1986; 17:648. 10. Petty GW, Brown RD Jr, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke 1999; 30:2513. 11. MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335:765. 12. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360:1903. 13. Kawachi I, Colditz GA, Stampfer MJ, et al. Smoking cessation and decreased risk of stroke in women. JAMA 1993; 269:232. 14. Kase CS, Caplan LR. Intracerebral Hemorrhage, Butterworth-Heinemann, Boston 1996. 15. Labovitz DL, Hauser WA, Sacco RL. Prevalence and predictors of early seizure and status epilepticus after first stroke. Neurology 2001; 57:200. 16. Caplan LR. Brain embolism. In: Practical Clinical Neurocardiology, Caplan LR, Chimowitz M, Hurst JW (Eds), Marcel Dekker, New York 1999. 17. Glass TA, Hennessey PM, Pazdera L, et al. Outcome at 30 days in the New England Medical Center Posterior Circulation Registry. Arch Neurol 2002; 59:369. 18. Sarkar S, Ghosh S, Ghosh SK, Collier A. Role of transcranial Doppler ultrasonography in stroke. Postgrad Med J 2007; 83:683. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 27/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate 19. Mart nez-S nchez P, Serena J, Alexandrov AV, et al. Update on ultrasound techniques for the diagnosis of cerebral ischemia. Cerebrovasc Dis 2009; 27 Suppl 1:9. 20. Saito K, Kimura K, Nagatsuka K, et al. Vertebral artery occlusion in duplex color-coded ultrasonography. Stroke 2004; 35:1068. 21. Caplan LR. Posterior Circulation Disease: Clinical Findings, Diagnosos, and Management, Bla ckwell Science, Boston 1996. 22. Dittrich R, Ritter MA, Droste DW. Microembolus detection by transcranial doppler sonography. Eur J Ultrasound 2002; 16:21. 23. Wilterdink JL, Furie KL, Easton JD. Cardiac evaluation of stroke patients. Neurology 1998; 51:S23. 24. Adams RJ, Chimowitz MI, Alpert JS, et al. Coronary risk evaluation in patients with transient ischemic attack and ischemic stroke: a scientific statement for healthcare professionals from the Stroke Council and the Council on Clinical Cardiology of the American Heart Association/American Stroke Association. Stroke 2003; 34:2310. 25. Touz E, Varenne O, Chatellier G, et al. Risk of myocardial infarction and vascular death after transient ischemic attack and ischemic stroke: a systematic review and meta-analysis. Stroke 2005; 36:2748. 26. Calvet D, Touz E, Varenne O, et al. Prevalence of asymptomatic coronary artery disease in ischemic stroke patients: the PRECORIS study. Circulation 2010; 121:1623. 27. Amarenco P, Lavall e PC, Labreuche J, et al. Prevalence of coronary atherosclerosis in patients with cerebral infarction. Stroke 2011; 42:22. 28. Powers WJ, Rabinstein AA, Ackerson T, 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; 50:e344. 29. Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014; 370:2478. 30. Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 2014; 370:2467. 31. Albers GW, Bernstein RA, Brachmann J, et al. Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report. J Am Heart Assoc 2016; 5:e002944. 32. Steinberg JS, Varma N, Cygankiewicz I, et al. 2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry. Heart Rhythm 2017; 14:e55. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 28/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate 33. Buck BH, Hill MD, Quinn FR, et al. Effect of Implantable vs Prolonged External Electrocardiographic Monitoring on Atrial Fibrillation Detection in Patients With Ischemic Stroke: The PER DIEM Randomized Clinical Trial. JAMA 2021; 325:2160. 34. Bernstein RA, Kamel H, Granger CB, et al. Effect of Long-term Continuous Cardiac Monitoring vs Usual Care on Detection of Atrial Fibrillation in Patients With Stroke Attributed to Large- or Small-Vessel Disease: The STROKE-AF Randomized Clinical Trial. JAMA 2021; 325:2169. 35. Kishore A, Vail A, Majid A, et al. Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis. Stroke 2014; 45:520. 36. Dussault C, Toeg H, Nathan M, et al. Electrocardiographic monitoring for detecting atrial fibrillation after ischemic stroke or transient ischemic attack: systematic review and meta- analysis. Circ Arrhythm Electrophysiol 2015; 8:263. 37. Afzal MR, Gunda S, Waheed S, et al. Role of Outpatient Cardiac Rhythm Monitoring in Cryptogenic Stroke: A Systematic Review and Meta-Analysis. Pacing Clin Electrophysiol 2015; 38:1236. 38. Wachter R, Gr schel K, Gelbrich G, et al. Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial. Lancet Neurol 2017; 16:282. 39. Israel C, Kitsiou A, Kalyani M, et al. Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders. Thromb Haemost 2017; 117:1962. 40. Tsivgoulis G, Katsanos AH, Grory BM, et al. Prolonged Cardiac Rhythm Monitoring and Secondary Stroke Prevention in Patients With Cryptogenic Cerebral Ischemia. Stroke 2019; 50:2175. 41. Tirschwell D, Akoum N. Detection of Subclinical Atrial Fibrillation After Stroke: Is There Enough Evidence to Treat? JAMA 2021; 325:2157. 42. Shimizu T, Takada T, Shimode A, et al. Association between paroxysmal atrial fibrillation and the left atrial appendage ejection fraction during sinus rhythm in the acute stage of stroke: a transesophageal echocardiographic study. J Stroke Cerebrovasc Dis 2013; 22:1370. 43. Warraich HJ, Gandhavadi M, Manning WJ. Mechanical discordance of the left atrium and appendage: a novel mechanism of stroke in paroxysmal atrial fibrillation. Stroke 2014; 45:1481. 44. Horowitz DR, Tuhrim S, Weinberger JM, et al. Transesophageal echocardiography: diagnostic and clinical applications in the evaluation of the stroke patient. J Stroke Cerebrovasc Dis 1997; 6:332. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 29/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate 45. Harloff A, Handke M, Reinhard M, et al. Therapeutic strategies after examination by transesophageal echocardiography in 503 patients with ischemic stroke. Stroke 2006; 37:859. 46. Markus HS, Hambley H. Neurology and the blood: haematological abnormalities in ischaemic stroke. J Neurol Neurosurg Psychiatry 1998; 64:150. 47. de Lau LM, Leebeek FW, de Maat MP, et al. Screening for coagulation disorders in patients with ischemic stroke. Expert Rev Neurother 2010; 10:1321. 48. Hankey GJ, Eikelboom JW, van Bockxmeer FM, et al. Inherited thrombophilia in ischemic stroke and its pathogenic subtypes. Stroke 2001; 32:1793. 49. Bushnell CD, Goldstein LB. Diagnostic testing for coagulopathies in patients with ischemic stroke. Stroke 2000; 31:3067. 50. Levine SR, Brey RL, Tilley BC, et al. Antiphospholipid antibodies and subsequent thrombo- occlusive events in patients with ischemic stroke. JAMA 2004; 291:576. 51. Janardhan V, Wolf PA, Kase CS, et al. Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack: the Framingham cohort and offspring study. Stroke 2004; 35:736. 52. Nojima J, Kuratsune H, Suehisa E, et al. Strong correlation between the prevalence of cerebral infarction and the presence of anti-cardiolipin/beta2-glycoprotein I and anti- phosphatidylserine/prothrombin antibodies Co-existence of these antibodies enhances ADP-induced platelet activation in vitro. Thromb Haemost 2004; 91:967. 53. Rothwell PM, Howard SC, Power DA, et al. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke. Stroke 2004; 35:2300. 54. Fibrinogen Studies Collaboration, Danesh J, Lewington S, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005; 294:1799. 55. Macellari F, Paciaroni M, Agnelli G, Caso V. Neuroimaging in intracerebral hemorrhage. Stroke 2014; 45:903. 56. Cucchiara B, Messe S, Sansing L, et al. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008; 39:2993. 57. Flaherty ML, Tao H, Haverbusch M, et al. Warfarin use leads to larger intracerebral hematomas. Neurology 2008; 71:1084. Topic 1083 Version 45.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 30/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate GRAPHICS Characteristics of stroke subtypes Stroke type Clinical course Risk factors Other clues Intracerebral Gradual onset and Hypertension, trauma, bleeding May be hemorrhage progression during diatheses, illicit drugs (eg, precipitated by minutes or hours in most patients, but may amphetamines, cocaine), vascular malformations. More common in sex or other physical activity. present abruptly with maximal deficit at onset. Black people and Asian people than in White people. Patient may have reduced alertness. Subarachnoid hemorrhage Abrupt onset of sudden, severe headache. Focal Smoking, hypertension, moderate to heavy alcohol use, genetic May be precipitated by brain dysfunction less susceptibility (eg, polycystic kidney sex or other common than with other types. disease, family history of subarachnoid hemorrhage) and physical activity. Patient may have sympathomimetic drugs (eg, cocaine) reduced alertness. Ischemic Stuttering progression Atherosclerotic risk factors (age, May have neck (thrombotic) with periods of improvement. Lacunes smoking, diabetes mellitus, etc). Males affected more commonly than bruit. develop over hours or at females. May have history of TIA. most a few days; large artery ischemia may evolve over longer periods. Ischemic Sudden onset with Atherosclerotic risk factors as listed Can be (embolic) deficit maximal at onset. Clinical findings may above. Males affected more commonly than females. History of precipitated by getting up at improve quickly. heart disease (valvular, atrial night to urinate fibrillation, endocarditis). or sudden coughing or sneezing. Graphic 69907 Version 5.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 31/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Headache and vomiting in stroke subtypes The frequency of sentinel headache, onset headache, and vomiting in three subtypes of stroke: subarachnoid hemorrhage, intraparenchymal (intracerebral) hemorrhage, and ischemic stroke. Onset headache was present in virtually all patients with SAH and about one-half of those with IPH; all of these symptoms were infrequent in patients with IS. SAH: subarachnoid hemorrhage; IPH: intraparenchymal (intracerebral) hemorrhage; IS: ischemic stroke. Data from: Gorelick PB, Hier DB, Caplan LR, Langenberg P. Headache in acute cerebrovascular disease. Neurology 1986; 36:1445. Graphic 60831 Version 4.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 32/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Pathophysiologic ischemic stroke classification Large vessel atherothrombotic stroke More common Bifurcation of the common carotid artery Siphon portion of the common carotid artery Middle cerebral artery stem Intracranial vertebral arteries proximal to middle basilar artery Origin of the vertebral arteries Less common Origin of the common carotid artery Posterior cerebral artery stem Origin of the major branches of the basilar-vertebral arteries Origin of the branches of the anterior, middle, and posterior cerebral arteries Small vessel (lacunar) stroke Mechanism Lipohyalinotic occlusion Less frequently proximal atherothrombotic occlusion Least likely embolic occlusion Most common locations Penetrating branches of the anterior, middle, and posterior cerebral and basilar arteries Cardioaortic embolic stroke Cardiac sources definite - antithrombotic therapy generally used Left atrial thrombus Left ventricular thrombus Atrial fibrillation and paroxysmal atrial fibrillation Sustained atrial flutter Recent myocardial infarction (within one month) Rheumatic mitral or aortic valve disease Bioprosthetic and mechanical heart valve Chronic myocardial infarction with ejection fraction <28 percent https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 33/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Symptomatic heart failure with ejection fraction <30 percent Dilated cardiomyopathy Cardiac sources definite - anticoagulation hazardous Bacterial endocarditis (exception nonbacterial) Atrial myxoma Cardiac sources possible Mitral annular calcification Patent foramen ovale Atrial septal aneurysm Atrial septal aneurysm with patent foramen ovale Left ventricular aneurysm without thrombus Isolated left atrial spontaneous echo contrast ("smoke") without mitral stenosis or atrial fibrillation Mitral valve strands Ascending aortic atheromatous disease (>4 mm) True unknown source embolic stroke Other Dissection Moyamoya Binswanger's disease Primary thrombosis Cerebral mass Graphic 55099 Version 4.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 34/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Acute stroke differential diagnosis Migraine aura Seizure with postictal paresis (Todd paralysis), aphasia, or neglect Central nervous system tumor or abscess Cerebral venous thrombosis Functional deficit (conversion reaction) Hypertensive encephalopathy Head trauma Mitochondrial disorder (eg, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes or MELAS) Multiple sclerosis Posterior reversible encephalopathy syndrome (PRES) Reversible cerebral vasoconstriction syndromes (RCVS) Spinal cord disorder (eg, compressive myelopathy, spinal dural arteriovenous fistula) Subdural hematoma Syncope Systemic infection Toxic-metabolic disturbance (eg, hypoglycemia, exogenous drug intoxication) Transient global amnesia Viral encephalitis (eg, herpes simplex encephalitis) Wernicke encephalopathy Graphic 69869 Version 7.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 35/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Eligibility criteria for the treatment of acute ischemic stroke with intravenous thrombolysis (recombinant tissue plasminogen activator or tPA) Inclusion criteria Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal or at neurologic baseline Age 18 years Exclusion criteria Patient history Ischemic stroke or severe head trauma in the previous three months Previous intracranial hemorrhage Intra-axial intracranial neoplasm Gastrointestinal malignancy Gastrointestinal hemorrhage in the previous 21 days Intracranial or intraspinal surgery within the prior three months Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic 185 mmHg or diastolic 110 mmHg) Active internal bleeding Presentation consistent with infective endocarditis Stroke known or suspected to be associated with aortic arch dissection Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic' Hematologic 3 Platelet count <100,000/mm * Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds* Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE) Current use (ie, last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays Head CT Evidence of hemorrhage https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 36/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Extensive regions of obvious hypodensity consistent with irreversible injury Warnings Only minor and isolated neurologic signs or rapidly improving symptoms Serum glucose <50 mg/dL (<2.8 mmol/L) Serious trauma in the previous 14 days Major surgery in the previous 14 days History of gastrointestinal bleeding (remote) or genitourinary bleeding Seizure at the onset of stroke with postictal neurologic impairments Pregnancy** Arterial puncture at a noncompressible site in the previous seven days Large ( 10 mm), untreated, unruptured intracranial aneurysm Untreated intracranial vascular malformation Additional warnings for treatment from 3 to 4.5 hours from symptom onset Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus ACS: acute coronary syndrome; aPTT: activated partial thromboplastin time; ECT: ecarin clotting time; INR: international normalized ratio; PT: prothrombin time; NIHSS: National Institutes of Health Stroke Scale; tPA: intravenous alteplase; TT: thrombin time; VTE: venous thromboembolism. Although it is desirable to know the results of these tests, thrombolytic therapy should not be delayed while results are pending unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia, (2) the patient is currently on or has recently received anticoagulants (eg, heparin, warfarin, a direct thrombin inhibitor, or a direct factor Xa inhibitor), or (3) use of anticoagulants is not known. Otherwise, treatment with intravenous tPA can be started before availability of coagulation test results but should be discontinued if the INR, PT, or aPTT exceed the limits stated in the table, or 3 if platelet count is <100,000 mm . With careful consideration and weighting of risk-to-benefit, patients may receive intravenous alteplase despite one or more warnings. Patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. Any of the following should be considered disabling deficits: Complete hemianopia: 2 on NIHSS question 3, or Severe aphasia: 2 on NIHSS question 9, or Visual or sensory extinction: 1 on NIHSS question 11, or Any weakness limiting sustained effort against gravity: 2 on NIHSS question 5 or 6, or Any deficits that lead to a total NIHSS >5, or https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 37/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Any remaining deficit considered potentially disabling in the view of the patient and the treating practitioner using clinical judgment Patients may be treated with intravenous alteplase if glucose level is subsequently normalized. The potential risks of bleeding with alteplase from injuries related to the trauma should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. The increased risk of surgical site bleeding with alteplase should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. There is a low increased risk of new bleeding with alteplase in the setting of past gastrointestinal or genitourinary bleeding. However, alteplase administration within 21 days of gastrointestinal bleeding is not recommended. Alteplase is reasonable in patients with a seizure at stroke onset if evidence suggests that residual impairments are secondary to acute ischemic stroke and not to a postictal phenomenon. * Alteplase can be given in pregnancy when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding. The safety and efficacy of administering alteplase is uncertain for these relative exclusions. Although these were exclusions in the trial showing benefit in the 3 to 4.5 hour window, intravenous alteplase appears to be safe and may be beneficial for patients with these criteria, including patients taking oral anticoagulants with an INR <1.7. Adapted from: 1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317. 2. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945. 3. Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:, Levine SR, Khatri P, et al. Review, historical context, and clari cations of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke 2013; 44:2500. 4. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scienti c rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 5. Powers WJ, Rabinstein AA, Ackerson T, 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; 50:e344. Graphic 71462 Version 26.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 38/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Time course of embolic stroke Embolic stroke occurs suddenly, with symptoms maximal at onset. This patient had multiple embolic events with different clinical symptoms (initially weakness, followed by paresthesias). Graphic 73261 Version 1.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 39/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Stuttering time course of thrombotic stroke The course of weakness of the right limb in a patient with a thrombotic stroke reveals fluctuating symptoms, varying between normal and abnormal, progressing in a stepwise or stuttering fashion with some periods of improvement. Graphic 64107 Version 2.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 40/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Time course of lacunar infarction Penetrating artery occlusions usually cause symptoms that develop over a short period of time, hours or at most a few days, compared to large artery-related brain ischemia which can evolve over a longer period. A stuttering course may ensue, as with large artery thrombosis. This patient had a pure motor hemiparesis. Graphic 52246 Version 1.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 41/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Time course of neurologic changes in intracerebral hemorrhage Schematic representation of rapid downhill course in terms of unusual behavior (solid line), hemimotor function (dotted line), and consciousness (dash-dotted line) in a patient with intracerebral (intraparenchymal) hemorrhage. Graphic 61491 Version 3.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 42/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Stroke mortality related to blood pressure and age Stroke mortality rate, pictured on a log scale with 95% CI, in each decade of age in relation to the estimated usual systolic and diastolic blood pressure at the start of that decade. Stroke mortality increases with both higher pressures and older ages. For diastolic pressure, each age-specific regression line ignores the left-hand point (ie, at slightly less than 75 mmHg) for which the risk lies significantly above the fitted regression line (as indicated by the broken line below 75 mmHg). CI: confidence interval. Data from Prospective Studies Collaboration, Lancet 2002; 360:1903. Graphic 66793 Version 5.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 43/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Major cerebral vascular territories Representation of the territories of the major cerebral vessels shown in a coronal section of the brain. Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases. Harrison's Principles of Internal Medicine, 13th ed, McGraw-Hill, New York 1994. Copyright 1994 McGraw-Hill Companies, Inc. Graphic 65199 Version 2.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 44/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Anterior cerebral artery distribution and signs and symptoms of occlusion Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases, Harrison's Principles of Internal Medicine, 13th ed. McGraw-Hill, New York 1994. Copyright 1994 McGraw-Hill Companies, Inc. Graphic 60945 Version 3.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 45/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Middle cerebral artery distribution and signs and symptoms of occlusion Reproduced with permission from Kistler JP, et al, Cerebrovascular Diseases, Harrison's Principles of Internal Medicine, 13th ed. McGraw-Hill, New York 1994. Copyright 1994 McGraw-Hill Companies, Inc. Graphic 81813 Version 2.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 46/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Posterior cerebral artery distribution and signs and symptoms of occlusion Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases, Harrison's Principles of Internal Medicine, 13th ed. McGraw-Hill, New York 1994. Copyright 1994 McGraw-Hill Companies, Inc. Graphic 60416 Version 2.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 47/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Inferior pontine syndrome Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases, Harrison's Principles of Internal Medicine, 13th ed. McGraw-Hill, New York 1994. Copyright 1994 McGraw-Hill Companies, Inc. Graphic 71587 Version 1.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 48/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Medullary syndrome Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases, Harrison's Principles of Internal Medicine, 13th ed. McGraw-Hill, New York 1994. Copyright 1994 McGraw-Hill Companies, Inc. Graphic 73073 Version 1.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 49/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Midpontine syndrome Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases, Harrison's Principles of Internal Medicine, 13th ed. McGraw-Hill, New York 1994. Copyright 1994 McGraw-Hill Companies, Inc. Graphic 68785 Version 1.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 50/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Acute ischemic stroke syndromes according to vascular territory Artery involved Syndrome Anterior cerebral artery Motor and/or sensory deficit (leg > face, arm) Grasp, sucking reflexes Abulia, paratonic rigidity, gait apraxia Middle cerebral artery Dominant hemisphere: aphasia, motor and sensory deficit (face, arm > leg > foot), may be complete hemiplegia if internal capsule involved, homonymous hemianopia Non-dominant hemisphere: neglect, anosognosia, motor and sensory deficit (face, arm > leg > foot), homonymous hemianopia Posterior cerebral artery Homonymous hemianopia; alexia without agraphia (dominant hemisphere); visual hallucinations, visual perseverations (calcarine cortex); sensory loss, choreoathetosis, spontaneous pain (thalamus); III nerve palsy, paresis of vertical eye movement, motor deficit (cerebral peduncle, midbrain) Penetrating vessels Pure motor hemiparesis (classic lacunar syndromes) Pure sensory deficit Pure sensory-motor deficit Hemiparesis, homolateral ataxia Dysarthria/clumsy hand Vertebrobasilar Cranial nerve palsies Crossed sensory deficits Diplopia, dizziness, nausea, vomiting, dysarthria, dysphagia, hiccup Limb and gait ataxia Motor deficit Coma Bilateral signs suggest basilar artery disease Internal carotid artery Progressive or stuttering onset of MCA syndrome, occasionally ACA syndrome as well if insufficient collateral flow Graphic 75487 Version 7.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 51/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Occlusion of middle and anterior cerebral arteries Reproduced with permission from: Netter, FH, Caplan, LR. Cerebrovascular Disease, Section III, Plate 8. In: The Netter Collection of Medical Illustrations, Vol 1, Nervous System, Part II, Neurologic and Neuromuscular Disorders, Netter, FH, Jones, HR, Dingle, RV (Eds), MediMedia USA, Inc 1986. Copyright 1986 Elsevier. Graphic 69630 Version 1.0 https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 52/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Contributor Disclosures Louis R Caplan, MD No relevant financial relationship(s) with ineligible companies to disclose. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 53/53